. . _:b6576691 "Although IL-22 has been reported to promote psoriasis-like skin alterations (Wolk et al., 2004; Wolk et al., >>2006<<; Zheng et al., 2007; Ma et al., 2008; Wolk et al., 2009), an increasing number of studies have reported a rather protective role of IL-22, especially in hepatitis and colitis experimental models (Zenewicz et al., 2007; Cella et al., 2008;" . _:b6576694 "Although IL-22 has been reported to promote psoriasis-like skin alterations (Wolk et al., 2004; Wolk et al., 2006; Zheng et al., 2007; Ma et al., 2008; Wolk et al., >>2009<<), an increasing number of studies have reported a rather protective role of IL-22, especially in hepatitis and colitis experimental models (Zenewicz et al., 2007; Cella et al., 2008; Satoh-Takayama et al., 2008; Sugimoto et al., 2008;" . _:b420373781 . . . _:b420373672 . . _:b420373546 . . _:b420373728 . _:b420373893 . _:b420373664 . . _:b420374021 . _:b420373561 . _:b420374020 . _:b420374042 . _:b6576691 . _:b420374023 . . _:b420374022 . _:b420374017 . . _:b420374016 . _:b420374034 . _:b6576705 "Furthermore, IL-22 induces the expression of antimicrobial peptides in epithelial cells (Liang et al., 2006; Aujla et al., 2007; Zheng et al., >>2008<<)." . _:b420374019 . _:b420374018 . _:b420374029 . _:b420373830 . _:b420374028 . _:b420374031 . . _:b420374030 . _:b420373489 . _:b420374025 . . _:b420374024 . _:b420373583 . . . _:b420374027 . . _:b420374026 . . _:b420374037 . _:b420374036 . _:b420374039 . _:b420374038 . _:b420374033 . _:b420373495 . _:b420374032 . . _:b6576693 . _:b420373849 . _:b420374035 . _:b6576675 "accordance with our data, several studies have demonstrated that MMP-2 and MMP-9 are up-regulated during active episodes of IBD in humans as well as in animal models of colitis (Baugh et al., 1998; Castaneda et al., 2005; Yen et al., >>2006<<; Gordon et al., 2008), and that IL-23 is able to induce their expression (Ivanov et al., 2007)." . _:b6576705 . _:b420374034 . _:b420373846 . _:b420373792 . _:b420374045 . . . _:b420374044 . . _:b420374047 . _:b420373602 . _:b420373525 . _:b420374046 . _:b420373825 . _:b420374041 . . _:b420374040 . _:b420373616 . _:b420374043 . _:b420374042 . _:b420373709 . . _:b420374053 . . _:b420374052 . _:b6576702 . _:b420374055 . . _:b420374054 . . _:b420373671 . _:b420374049 . . _:b420374048 . _:b420374051 . _:b420374050 . . . . _:b420374057 . _:b420373887 . _:b420374056 . . _:b420373898 . _:b420374058 . _:b420373942 . _:b420373903 . . _:b6576660 . _:b420374051 . . . . . _:b420374011 . . _:b6576667 . _:b420374056 . . . _:b420373897 . . . _:b420373718 . _:b6576672 . . _:b420373916 . . _:b420373725 . . _:b420373749 . . _:b420373904 . _:b420373833 . _:b6576717 "However, flow cytometry did not associate IL-22 production with NK cells, as recently described (Cella et al., 2008; Luci et al., >>2008<<; Sanos et al., 2009; Satoh-Takayama et al., 2008; Zenewicz et al., 2008)." . _:b420374006 . _:b420373980 . . . _:b420373540 . _:b420373888 . . _:b420373890 . . _:b420373653 . _:b420373640 . _:b420373798 . . _:b420373996 . . _:b420373509 . . . . . . . _:b420373549 . . . . . _:b420373611 . . . _:b420373894 . . . _:b6576673 . _:b420373686 . _:b6576684 "In agreement with our data, several studies have demonstrated that IL-17 and IL-22 possess distinct roles during immune responses (Cruz et al., 2006; Kreymborg et al., >>2007<<; Schulz et al., 2008; Sugimoto et al., 2008; Wolk et al., 2009)." . _:b420373814 . _:b420373906 . . _:b420373524 . _:b6576707 "Lastly, pathogenic IL-22\u2013producing cells might constitute a subpopulation of cells, different from Th17 and NK22 cells. IL-22 production is higher in Th1 cells than in Th17 cells (Volpe et al., >>2008<<), and a unique IL-22\u2013producing population of NKp46+ROR\u03B3t+ natural killer cells, termed NK22 cells, was identified in the dermis, lamina propria, and other mucosa-associated lymphoid tissues (Cella et al., 2008; Luci et al., 2008; Sanos et" . . . _:b420373724 . _:b420373557 . _:b6576661 "For peroral infection, mice were infected with 100 cysts in a volume of 0.3 ml in PBS (pH 7.4) by gavage, as described previously (Heimesaat et al., >>2006<<)." . . _:b420373706 . _:b420373486 . _:b420373867 . . _:b6576662 "Histological scores and parasite loads were determined in fixed and paraffin-embedded tissue sections taken from the terminal ileum, as previously described (Heimesaat et al., >>2006<<)." . _:b420374035 . . _:b420373909 . . _:b420373973 . _:b420373747 . . _:b420374021 "2"^^ . . _:b420374020 "2"^^ . . _:b420374023 "2"^^ . _:b420373566 . _:b420374022 "2"^^ . _:b420374017 "2"^^ . . _:b420374016 "2"^^ . _:b420374019 "2"^^ . _:b420373627 . _:b420374016 . _:b420373517 . _:b420374018 "2"^^ . _:b420374029 "2"^^ . _:b420373507 . _:b420373712 . _:b420374028 "2"^^ . _:b420374031 "2"^^ . _:b420374030 "2"^^ . _:b420373807 . _:b420374025 "2"^^ . _:b420374024 "2"^^ . _:b420374027 "2"^^ . _:b420373921 . _:b420373758 . _:b420374026 "2"^^ . _:b420374037 "2"^^ . _:b420374036 "2"^^ . _:b420373699 . _:b420374039 "2"^^ . . . . _:b420374038 "2"^^ . . _:b420374033 "2"^^ . . _:b420373698 . _:b420374032 "2"^^ . _:b420374035 "2"^^ . _:b420374034 "2"^^ . _:b420374045 "2"^^ . . _:b420374044 "2"^^ . _:b6576697 "al., 2008; Wolk et al., 2009), an increasing number of studies have reported a rather protective role of IL-22, especially in hepatitis and colitis experimental models (Zenewicz et al., 2007; Cella et al., 2008; Satoh-Takayama et al., >>2008<<; Sugimoto et al., 2008; Zenewicz et al., 2008)." . _:b420374047 "2"^^ . _:b420373829 . _:b420374046 "2"^^ . . . _:b420373786 . _:b420374041 "2"^^ . . . . . . _:b420374040 "2"^^ . . _:b420374043 "2"^^ . _:b420373751 . _:b420374042 "2"^^ . _:b420374053 "2"^^ . _:b420374052 "2"^^ . _:b420374055 "2"^^ . _:b420374054 "2"^^ . _:b420374049 "2"^^ . _:b420374048 "2"^^ . _:b420373915 . _:b420374051 "2"^^ . . _:b420373720 . _:b420374050 "2"^^ . _:b420374053 . _:b420373834 . . _:b6576663 . _:b420373972 . _:b420374057 "2"^^ . _:b420374056 "2"^^ . . _:b420374058 "2"^^ . . _:b420374027 . . . _:b420373510 . _:b420373499 . _:b420374039 . . _:b420373843 . . . _:b420374038 . . _:b420373752 . _:b6576714 "Furthermore, a human Th cell population that secretes IL-22 but not IL-17 nor IFN-\u03B3 has been recently reported (Duhen et al., 2009; Trifari et al., >>2009<<). In the present study, we used a well-characterized IL-22 mAb (Zheng et al., 2007) to identify the source of IL-22 after ileitis induction. CD4+ T cells were the predominant source of IL-22. IL-17 was down-regulated and dispensable for" . . _:b420373511 . _:b420373933 . _:b420373695 . . . . . _:b420374028 . _:b420373588 . _:b420374013 . _:b420374052 . _:b420373947 . _:b420373501 . _:b420373612 . _:b420373586 . . _:b420374047 . _:b420373491 . . . _:b420373493 . . _:b420373984 . _:b420374003 . _:b420373745 . . _:b420373621 . _:b6576681 . . . _:b420373705 . _:b420373564 . . . _:b420373774 . _:b420373560 . . . . _:b420373551 . _:b420373765 . _:b420373669 . . _:b420373764 . _:b420373729 . _:b420373767 . _:b420373766 . _:b420373743 . _:b420373761 . _:b420373541 . _:b420373760 . . _:b420373763 . _:b420373928 . _:b420373762 . _:b420373680 . _:b420373773 . . _:b420373772 . . _:b420373775 . _:b420373774 . _:b420373769 . _:b420373845 . _:b6576693 "Although IL-22 has been reported to promote psoriasis-like skin alterations (Wolk et al., 2004; Wolk et al., 2006; Zheng et al., 2007; Ma et al., >>2008<<; Wolk et al., 2009), an increasing number of studies have reported a rather protective role of IL-22, especially in hepatitis and colitis experimental models (Zenewicz et al., 2007; Cella et al., 2008; Satoh-Takayama et al., 2008;" . _:b420373768 . . _:b420373771 . _:b420373994 . . _:b420373770 . _:b420373781 . . _:b420374007 . _:b420373780 . _:b420373783 . _:b420373597 . _:b420373835 . _:b420373782 . _:b420373777 . _:b420373594 . _:b420373776 . _:b420373779 . _:b420373871 . _:b420373778 . _:b420373666 . _:b420373516 . . _:b420373789 . . _:b420373788 . _:b420373791 . . _:b420373790 . . _:b420373785 . _:b420373784 . _:b420373787 . _:b420373786 . _:b420373868 . _:b420373797 . . _:b420373796 . _:b6576690 . _:b420373799 . _:b420373798 . . _:b6576683 "In agreement with our data, several studies have demonstrated that IL-17 and IL-22 possess distinct roles during immune responses (Cruz et al., >>2006<<; Kreymborg et al., 2007; Schulz et al., 2008; Sugimoto et al., 2008; Wolk et al., 2009)." . . _:b420373793 . . _:b420373792 . _:b420373795 . _:b420373794 . _:b420373805 . _:b420373703 . . _:b420373804 . _:b420373702 . _:b420373807 . _:b420373656 . . _:b420373806 . . _:b420373647 . _:b420373801 . _:b420373800 . _:b420373803 . _:b420373802 . . . _:b420373813 . _:b6576667 "results" . _:b420373812 . _:b420373815 . _:b420373873 . _:b420373814 . _:b420373809 . . _:b420373808 . _:b420373811 . _:b420373810 . . _:b420373821 . . _:b420373820 . _:b420373823 . _:b420373822 . _:b420373619 . _:b420373817 . _:b420373931 . _:b420373816 . _:b420373756 . _:b420373819 . _:b420373818 . . _:b420373829 . _:b420373828 . _:b6576660 "materials and methods" . _:b420373831 . _:b420373830 . . . _:b420373825 . _:b420373824 . _:b420373649 . . . _:b420373827 . . _:b420373826 . _:b420373837 . . _:b420373625 . _:b420373836 . _:b6576695 . _:b420373839 . . . _:b420373838 . _:b420373544 . _:b420373833 . _:b420373832 . _:b6576721 . _:b6576668 . _:b420373667 . _:b420373835 . _:b420373547 . . _:b420373834 . _:b420373845 . _:b420373844 . _:b420373678 . _:b420373847 . _:b420374026 . _:b420373846 . _:b6576719 . _:b420373711 . _:b420373548 . _:b420373900 . _:b420373841 . . _:b420373784 . _:b420373840 . _:b420373682 . . _:b420373843 . _:b420373842 . . _:b420373853 . . _:b420373852 . _:b420373855 . _:b420373854 . _:b6576711 . _:b420373849 . . _:b420373848 . . _:b420373851 . _:b420373593 . _:b6576677 "during active episodes of IBD in humans as well as in animal models of colitis (Baugh et al., 1998; Castaneda et al., 2005; Yen et al., 2006; Gordon et al., 2008), and that IL-23 is able to induce their expression (Ivanov et al., >>2007<<). Epithelial barrier dysfunction may be involved in the MMP-mediated effects in T. gondii\u2013induced ileitis, because MMP-2\u2212/\u2212 mice showed a lower rate of bacterial translocation into the spleen compared with WT mice (unpublished data)." . _:b420373850 . _:b420373539 . _:b420373861 . _:b420373860 . _:b6576701 . _:b420373885 . _:b420373863 . _:b420373862 . . _:b420373857 . _:b420373856 . _:b6576697 . _:b6576678 "Dosages of RO28-2653 used in the present study were similar to those administered in pharmacodynamic studies in rat and mouse models (Kilian et al., >>2006<<; Abramjuk et al., 2007)." . _:b420373944 . _:b420373859 . . _:b420373858 . _:b420373746 . . _:b420373796 . _:b420373869 . . "10.1084%2Fjem.20090900" . _:b420373868 . _:b420374049 . _:b420373871 . _:b420373870 . _:b420373907 . _:b420373865 . . . _:b420373864 . _:b420373727 . _:b420373867 . . _:b420373866 . _:b420373762 . _:b420373877 . _:b420373644 . _:b420373847 . _:b420373876 . _:b420373879 . _:b420373878 . _:b420373794 . _:b420373873 . _:b420373512 . _:b420373872 . _:b420373875 . _:b420373734 . _:b420373874 . _:b420373885 . _:b420374012 . _:b420373884 . . _:b6576706 . _:b420373887 . . _:b420373886 . _:b420373739 . . . _:b420373881 . _:b6576718 "However, flow cytometry did not associate IL-22 production with NK cells, as recently described (Cella et al., 2008; Luci et al., 2008; Sanos et al., >>2009<<; Satoh-Takayama et al., 2008; Zenewicz et al., 2008)." . _:b420373694 . _:b420373880 . _:b420373883 . _:b6576660 . _:b420373882 . _:b420373567 . _:b6576661 . _:b420373893 . _:b420373688 . _:b420373858 . _:b6576662 . _:b420373707 . . _:b420373892 . _:b6576663 . _:b420373895 . _:b6576709 . _:b420373894 . _:b420373651 . _:b420373889 . _:b420373532 . _:b420373591 . _:b420373953 . . _:b420373587 . _:b6576710 . _:b420373888 . . _:b420373659 . _:b420373891 . . _:b6576668 . _:b420373890 . _:b420373965 . _:b6576669 . _:b420373901 . _:b420373748 . _:b6576670 . _:b420373900 . . _:b6576671 . _:b420373790 . . _:b6576717 . _:b420373903 . _:b6576664 . _:b420373902 . _:b6576665 . _:b420373897 . _:b420373696 . _:b6576666 . _:b6576718 . _:b420373896 . . . "PMC0" . _:b420374022 . _:b6576667 . _:b420373960 . _:b420373899 . _:b6576676 . _:b420373558 . _:b420373898 . . _:b6576692 . _:b6576677 . _:b420373909 . _:b6576678 . _:b6576689 . _:b420373719 . _:b420373908 . _:b6576679 . _:b420373998 . _:b420373977 . _:b420373911 . _:b420373788 . _:b420373901 . . _:b6576672 . _:b420373910 . _:b6576673 . _:b420374032 . _:b420373905 . _:b420373738 . _:b420373689 . _:b6576674 . _:b420373755 . . _:b420373904 . . _:b6576675 . _:b420373907 . _:b420373759 . . _:b6576684 . _:b420373906 . _:b6576685 . _:b420373917 . _:b6576715 . _:b6576686 . _:b420373916 . _:b6576687 . _:b420373919 . _:b6576680 . . _:b420373918 . _:b6576681 . _:b420373913 . . _:b6576682 . _:b420373912 . _:b6576683 . _:b420373915 . _:b6576692 . _:b420373914 . _:b6576693 . _:b420373925 . . _:b6576694 . _:b420373924 . . _:b6576695 . _:b420373842 . _:b420373927 . _:b420373486 "39"^^ . . _:b6576688 . _:b420373489 "21"^^ . _:b420373926 . _:b420373526 . _:b6576689 . _:b420373921 . _:b420373491 "19"^^ . _:b420373488 "24"^^ . _:b6576690 . _:b420373823 . _:b420373920 . _:b420373487 "32"^^ . _:b6576691 . . _:b420373490 "21"^^ . . _:b420373923 . _:b6576700 . _:b420373922 . _:b420373492 "19"^^ . _:b420373493 "16"^^ . _:b6576701 . _:b420373645 . _:b420373933 . _:b420373494 "16"^^ . _:b6576702 . _:b420373932 . _:b420373495 "15"^^ . _:b6576703 . _:b420373935 . _:b420373496 "15"^^ . _:b6576683 . _:b6576696 . _:b420373503 "13"^^ . _:b420373497 "14"^^ . _:b420373934 . _:b6576697 . _:b420373498 "14"^^ . _:b420373929 . _:b6576684 . _:b6576698 . _:b420373499 "14"^^ . _:b420373928 . _:b6576699 . _:b420373500 "14"^^ . . _:b420373931 . _:b6576708 . _:b420373501 "14"^^ . _:b420373930 . _:b420373760 . _:b6576709 . _:b420373502 "14"^^ . _:b420373941 . _:b6576710 . _:b420373987 . _:b420373940 . _:b6576711 . _:b6576690 "Although IL-22 has been reported to promote psoriasis-like skin alterations (Wolk et al., >>2004<<; Wolk et al., 2006; Zheng et al., 2007; Ma et al., 2008; Wolk et al., 2009), an increasing number of studies have reported a rather protective role of IL-22, especially in hepatitis and colitis experimental models (Zenewicz et al., 2007;" . _:b420373943 . _:b6576704 . _:b420373942 . _:b6576705 . _:b420373937 . . _:b6576706 . _:b420373936 . . _:b6576707 . _:b420373494 . _:b420373939 . _:b6576716 . _:b420373938 . _:b6576717 . . _:b420373949 . _:b6576718 . _:b420373853 . _:b420374019 . _:b420373948 . _:b6576719 . _:b420373951 . _:b6576712 . _:b420373950 . _:b420374043 . _:b6576713 . _:b420373945 . . _:b6576714 . _:b420373944 . _:b6576677 . _:b6576715 . _:b420373947 . _:b420373946 . _:b420373957 . . . _:b420373731 . _:b420373956 . _:b420373715 . _:b420373911 . _:b420373580 . . _:b420373959 . _:b6576720 . _:b420373958 . _:b6576721 . _:b420373953 . _:b6576707 . _:b420373638 . _:b420374004 . _:b420373952 . . . _:b420373955 . _:b6576719 "However, flow cytometry did not associate IL-22 production with NK cells, as recently described (Cella et al., 2008; Luci et al., 2008; Sanos et al., 2009; Satoh-Takayama et al., >>2008<<; Zenewicz et al., 2008)." . _:b420373954 . _:b420373965 . _:b420374000 . _:b420373964 . . . _:b420373967 . _:b6576678 . _:b420373966 . _:b420373961 . _:b420373531 . _:b420373960 . _:b420373963 . . . _:b420373962 . _:b420373973 . _:b6576702 "mice from colitis in a CD45RBhi transfer model (Zenewicz et al., 2008), and IL-22 deficiency rendered mice susceptible to Citrobacter rodentium\u2013 and dextran sulfate sodium\u2013induced colitis (Satoh-Takayama et al., 2008; Zheng et al., >>2008<<). Furthermore, IL-22 induces the expression of antimicrobial peptides in epithelial cells (Liang et al., 2006; Aujla et al., 2007; Zheng et al., 2008)." . _:b420373972 . _:b420373975 . _:b420373974 . _:b420373508 . . _:b420373929 . _:b420373969 . _:b420373803 . _:b420373968 . _:b420373971 . . _:b420373970 . . _:b420373981 . . _:b420373836 . _:b420373980 . . _:b420373983 . _:b420374050 . _:b6576687 . _:b420373982 . . _:b420373977 . _:b420373976 . . . _:b420373979 . . _:b420373978 . . _:b420373989 . _:b420373988 . _:b420373991 . _:b420373990 . _:b420373985 . _:b6576694 . _:b420373646 . _:b420373939 . _:b420373984 . _:b420373932 . . _:b420373987 . . _:b420373986 . _:b420373576 . _:b420373997 . . . _:b420373996 . _:b420373581 . _:b420374037 . . _:b420373999 . . . _:b420373998 . _:b420373876 . _:b420373993 . _:b420373854 . _:b420373992 . _:b420373878 . _:b420373862 . _:b420373995 . _:b420373994 . _:b6576695 "Wolk et al., 2006; Zheng et al., 2007; Ma et al., 2008; Wolk et al., 2009), an increasing number of studies have reported a rather protective role of IL-22, especially in hepatitis and colitis experimental models (Zenewicz et al., >>2007<<; Cella et al., 2008; Satoh-Takayama et al., 2008; Sugimoto et al., 2008; Zenewicz et al., 2008)." . . _:b420374005 . _:b420374004 . _:b420373732 . _:b420373600 . _:b420374007 . _:b420373626 . _:b420374006 . . . _:b420374001 . _:b420374000 . . _:b420374029 . _:b420374003 . _:b420373504 . _:b420374002 . _:b420373809 . _:b420374013 . _:b420374012 . _:b420374015 . _:b420373570 . _:b420373812 . _:b420374014 . _:b420374009 . . . _:b420374008 . _:b420374011 . _:b420374010 . _:b420373509 . _:b420373508 . _:b420373511 . _:b420373565 . _:b420373510 . _:b420373542 . _:b420373505 . _:b420373504 . _:b420373507 . _:b420373506 . . . . _:b420373517 . _:b6576669 "Given that MMPs have been proposed to play an important role in the pathology of IBD (Gao et al., >>2005<<), we determined the enzymatic activity of gelatinases A (MMP-2) and B (MMP-9) in the small intestine of T. gondii\u2013infected WT mice using gelatin zymography." . _:b420373516 . _:b420373771 . _:b420373852 . _:b420373954 . _:b420373658 . _:b420373519 . _:b420373505 . _:b420373572 . _:b6576662 . _:b420373518 . . _:b6576661 . . _:b420373513 . . . . . _:b420373512 . _:b420373735 . _:b420374057 . . _:b420373912 . _:b420373800 . _:b420373522 . _:b420373515 . _:b420373514 . . _:b420373525 . . _:b420373841 . _:b420373681 . _:b420373524 . _:b420373527 . _:b6576670 . _:b420373526 . _:b420373951 . _:b420373521 . _:b420373520 . _:b420373523 . _:b420373585 . _:b6576666 . . _:b420373522 . . _:b6576665 . . _:b420373533 . _:b420373859 . _:b420373532 . _:b420374018 . _:b420373535 . _:b420373534 . _:b420373535 . . . _:b420374046 . _:b420373514 . _:b420373529 . . _:b420373528 . _:b420373968 . . . _:b420373531 . _:b420373883 . _:b420373530 . _:b420373541 . _:b420374001 . . _:b420373540 . _:b420373872 . . _:b420373543 . _:b420373542 . _:b420373537 . _:b420373536 . . _:b6576700 "In regard to intestinal inflammation, IL-22 protected mice from colitis in a CD45RBhi transfer model (Zenewicz et al., >>2008<<), and IL-22 deficiency rendered mice susceptible to Citrobacter rodentium\u2013 and dextran sulfate sodium\u2013induced colitis (Satoh-Takayama et al., 2008; Zheng et al., 2008)." . _:b420373642 . _:b420373539 . . _:b420373538 . _:b420373523 . _:b420373549 . . _:b420373879 . _:b420373548 . . . _:b420373559 . _:b6576672 "discussion" . _:b420373551 . _:b6576713 . . _:b420373550 . _:b420373545 . _:b6576714 . _:b420373777 . _:b420373544 . . _:b420373547 . . . . _:b420373976 . _:b420373546 . . _:b420373701 . _:b420373557 . . _:b420373652 . _:b420373556 . _:b420373927 . _:b420373559 . . _:b420374054 . _:b420373550 . _:b420373558 . . . _:b420373553 . _:b6576670 "Lastly, we examined IL-22 levels in the ilea of infected gnotobiotic mice, because we have previously shown that these mice do not develop ileitis after T. gondii infection (Heimesaat et al., >>2006<<). Interestingly, IL-22 was almost undetectable in infected gnotobiotic mice, whereas mice with a normal specific pathogen-free gut flora had significantly higher IL-22 levels in their ilea 8 d after infection (Fig." . _:b420373552 . . . _:b420373555 . _:b420373554 . _:b6576680 "Although nonselective MMP-blocking agents may cause severe adverse side effects (Bernardo et al., >>2002<<), RO28-2653 did not show major side effects in rat and monkey toxicological studies (unpublished data)." . _:b420373565 . _:b420373966 . _:b420373564 . _:b420373567 . _:b420373818 . . _:b420373869 . . . . _:b420373566 . _:b420373561 . _:b420373560 . _:b420373563 . . _:b420373562 . _:b420373573 . _:b420373572 . _:b420373575 . _:b420373860 . . . _:b420373574 . . _:b420373569 . . . _:b420373797 . _:b420373568 . _:b420373863 . . . . . _:b420373571 . _:b420373820 . _:b420373570 . _:b6576692 "Although IL-22 has been reported to promote psoriasis-like skin alterations (Wolk et al., 2004; Wolk et al., 2006; Zheng et al., >>2007<<; Ma et al., 2008; Wolk et al., 2009), an increasing number of studies have reported a rather protective role of IL-22, especially in hepatitis and colitis experimental models (Zenewicz et al., 2007; Cella et al., 2008; Satoh-Takayama et" . _:b420373636 . _:b420373581 . _:b420373773 . . _:b420373580 . . _:b420373685 . . _:b420373583 . _:b420373582 . _:b420373577 . _:b420374010 . _:b420373576 . . . _:b420373579 . . . _:b420373578 . _:b420373589 . _:b420373588 . . _:b420373591 . _:b420374021 . . _:b420373590 . . _:b420373585 . _:b420373584 . . _:b420373587 . _:b420373586 . . _:b420373597 . . _:b420373920 . _:b420373596 . . _:b420373599 . . _:b6576708 "cells (Volpe et al., 2008), and a unique IL-22\u2013producing population of NKp46+ROR\u03B3t+ natural killer cells, termed NK22 cells, was identified in the dermis, lamina propria, and other mucosa-associated lymphoid tissues (Cella et al., >>2008<<; Luci et al., 2008; Sanos et al., 2009; Satoh-Takayama et al., 2008; Zenewicz et al., 2008)." . _:b420373598 . _:b420373593 . _:b6576676 . _:b420373832 . _:b420373592 . _:b420373595 . _:b420373594 . _:b420373866 . _:b420373629 . _:b420373605 . _:b420373604 . _:b420373787 . . _:b420373938 . _:b420373607 . _:b420373606 . . _:b420373633 . _:b6576720 "However, flow cytometry did not associate IL-22 production with NK cells, as recently described (Cella et al., 2008; Luci et al., 2008; Sanos et al., 2009; Satoh-Takayama et al., 2008; Zenewicz et al., >>2008<<). We cannot formally rule out the presence of NK22 cells, because the mAb used to detect IL-22\u2013producing cells may have failed to detect IL-22 secretion by non\u2013T cells because of a short half-life of IL-22 or a low sensitivity of this mAb." . _:b420373601 . _:b420373600 . . _:b420373603 . _:b420373602 . _:b420373613 . _:b420373641 . . _:b420373612 . _:b420373615 . . _:b420373614 . _:b420373609 . . . . _:b420373608 . _:b6576698 "2009), an increasing number of studies have reported a rather protective role of IL-22, especially in hepatitis and colitis experimental models (Zenewicz et al., 2007; Cella et al., 2008; Satoh-Takayama et al., 2008; Sugimoto et al., >>2008<<; Zenewicz et al., 2008)." . _:b420373611 . _:b420374005 . _:b420373610 . _:b420373621 . _:b6576688 . _:b420373620 . _:b420373623 . . _:b420373622 . _:b420373910 . _:b420373617 . . . . _:b420373616 . _:b420373619 . _:b420373840 . _:b420373618 . . . _:b420373629 . . _:b420373628 . . _:b420373631 . . _:b420373630 . . . _:b420373625 . _:b420373624 . _:b6576715 "In the present study, we used a well-characterized IL-22 mAb (Zheng et al., >>2007<<) to identify the source of IL-22 after ileitis induction." . _:b420373627 . _:b420373626 . _:b420373637 . _:b420373744 . . _:b420373636 . _:b6576666 "mg/liter vancomycin (Cell Pharm), 200 mg/liter ciprofloxacin (Bayer Vital), 250 mg/liter imipenem (MSD), and 1 g/liter metronidazole (Fresenius) to the drinking water ad libitum for 6\u20138 wk, as described previously (Heimesaat et al., >>2006<<)." . _:b420373670 . _:b420373639 . . _:b420373582 . _:b420373638 . . _:b420373633 . _:b420373632 . _:b420373635 . . . _:b420373634 . . _:b420373772 . . _:b420373645 . _:b420373967 . _:b420373644 . _:b420373647 . . . . _:b420373646 . . . _:b420373641 . . _:b420373640 . _:b420373511 "11"^^ . . _:b420373643 . _:b420373889 . . _:b420373510 "11"^^ . _:b420373642 . _:b420373804 . _:b420373509 "12"^^ . _:b420373653 . _:b420373693 . _:b6576698 . _:b420373508 "12"^^ . _:b420373652 . _:b420373584 . . _:b420373507 "12"^^ . _:b420373655 . _:b420373568 . _:b420373506 "12"^^ . . _:b420373654 . . _:b420373505 "12"^^ . . _:b420373649 . _:b420373504 "12"^^ . _:b420373648 . . _:b420373651 . _:b420373518 "10"^^ . . _:b420373519 "9"^^ . _:b420373650 . _:b420373517 "10"^^ . . . _:b420373991 . . _:b420373661 . _:b420373516 "10"^^ . _:b420373660 . . _:b420373515 "11"^^ . . . _:b420373663 . _:b420373514 "11"^^ . _:b420373662 . _:b420373941 . _:b420373513 "11"^^ . _:b420373657 . _:b420373512 "11"^^ . _:b420373656 . _:b420373526 "9"^^ . _:b420373659 . _:b6576703 . _:b420373527 "9"^^ . _:b420373658 . _:b420373524 "9"^^ . _:b420373669 . . _:b420373668 . _:b420373742 . _:b420373525 "9"^^ . _:b420373632 . _:b420373882 . . _:b420373671 . _:b420373522 "9"^^ . _:b420373895 . . _:b420373918 . _:b420373523 "9"^^ . _:b420373670 . . _:b420373520 "9"^^ . _:b420373665 . _:b6576686 . _:b420373521 "9"^^ . _:b420373664 . _:b420374045 . _:b420373496 . _:b420373534 "8"^^ . _:b420373667 . _:b420373535 "8"^^ . _:b420373666 . _:b420373532 "8"^^ . . _:b420373577 . _:b420373677 . _:b420373923 . _:b420373533 "8"^^ . _:b420373875 . _:b420373676 . _:b420373943 . . _:b420373679 . _:b420373530 "9"^^ . _:b420373531 "8"^^ . _:b420373678 . . _:b420373534 . _:b420373992 . _:b420373673 . _:b420373528 "9"^^ . . _:b420374048 . _:b420373529 "9"^^ . _:b420373672 . . _:b420373542 "8"^^ . . _:b420373675 . _:b420373543 "7"^^ . _:b420373674 . . _:b420373540 "8"^^ . . _:b420373685 . _:b420373986 . _:b420373541 "8"^^ . _:b420374025 . _:b420373684 . _:b420373902 . _:b420373538 "8"^^ . _:b420373919 . _:b420373687 . _:b420373539 "8"^^ . _:b420373686 . _:b420373795 . _:b420373536 "8"^^ . _:b420373886 . _:b420373681 . _:b420373537 "8"^^ . . _:b420373680 . . _:b420373550 "6"^^ . _:b420373628 . . _:b420373683 . _:b420373914 . _:b420373761 . _:b420373551 "6"^^ . . _:b420373682 . _:b420373548 "6"^^ . _:b6576663 "gondii IgG antibody and counted in the terminal ileum, as previously described (Vossenk\u00E4mper et al., >>2004<<)." . _:b420373700 . . _:b420373693 . _:b420373549 "6"^^ . . _:b420373692 . _:b420373546 "7"^^ . _:b420373865 . _:b420373695 . _:b420373547 "7"^^ . _:b420373615 . _:b6576671 "Given the evidence that both T cells and non\u2013T cells can produce IL-22 (Wolk and Sabat, >>2006<<), we investigated the potential source of IL-22 in the ileum of mice after ileitis induction." . _:b420373694 . _:b420373763 . _:b420373544 "7"^^ . _:b420373952 . _:b420373689 . . _:b420373545 "7"^^ . . _:b420373688 . _:b420373558 "6"^^ . _:b420373827 . _:b420373691 . _:b420373559 "6"^^ . _:b420373958 . . _:b420373533 . _:b420373690 . _:b420373529 . _:b420373556 "6"^^ . _:b420373701 . _:b420373557 "6"^^ . . _:b420373700 . . _:b420373554 "6"^^ . _:b420373703 . _:b420373555 "6"^^ . _:b420373702 . _:b420373552 "6"^^ . _:b420373697 . _:b420373553 "6"^^ . _:b420373696 . _:b420374031 . _:b420373566 "6"^^ . _:b420373699 . _:b420373757 . _:b420373698 . _:b420373564 "6"^^ . . _:b420373567 "5"^^ . _:b420373709 . _:b420373565 "6"^^ . _:b420373617 . _:b420373708 . _:b420373562 "6"^^ . . _:b420373711 . _:b420373563 "6"^^ . _:b420373710 . _:b420373560 "6"^^ . _:b420373705 . _:b420373561 "6"^^ . _:b420373704 . _:b420373819 . _:b420373569 . _:b420373573 "5"^^ . _:b420373707 . _:b420373572 "5"^^ . _:b420373706 . . _:b420373905 . _:b420373575 "5"^^ . _:b420373717 . _:b420373657 . _:b420373945 . . _:b420373574 "5"^^ . _:b420373716 . _:b420373606 . _:b420373569 "5"^^ . _:b420373719 . _:b420373568 "5"^^ . _:b420373718 . _:b420373571 "5"^^ . _:b420373713 . _:b420373543 . . _:b420373712 . _:b420373570 "5"^^ . _:b420373581 "5"^^ . _:b420373715 . . _:b420373993 . _:b420373580 "5"^^ . _:b420373714 . _:b420373583 "5"^^ . _:b420373725 . _:b420373582 "5"^^ . _:b420373724 . _:b420373599 . . _:b420373577 "5"^^ . _:b420373727 . _:b420373576 "5"^^ . _:b420373726 . _:b420373579 "5"^^ . _:b420373721 . _:b420373837 . . _:b420373578 "5"^^ . _:b420373720 . . _:b420373589 "5"^^ . _:b420373723 . _:b420373983 . _:b6576664 "mRNA was reverse transcribed and analyzed in triplicate assays by TaqMan PCR using a sequence detection system (ABI Prism 7700; Applied Biosystems), as described previously (Wolk et al., >>2002<<). For detection of mouse IFN-\u03B3, IL-12, IL-10, IL-6, IL-1\u03B2, IL-17A, IL-22, MMP-2, MMP-9, and IL-23p19, assays including double-fluorescent probes in combination with assays for the mouse housekeeping gene hypoxanthine" . _:b420373588 "5"^^ . _:b420373722 . _:b420373971 . _:b420373591 "4"^^ . _:b420373733 . _:b420373753 . _:b420373590 "4"^^ . _:b420373963 . _:b420373732 . _:b420373896 . _:b420373585 "5"^^ . _:b420373735 . _:b420373838 . _:b420373506 . _:b420373584 "5"^^ . _:b420373734 . _:b420373587 "5"^^ . _:b420373729 . _:b420373586 "5"^^ . _:b420373728 . . . _:b420373597 "4"^^ . _:b420373731 . . _:b420373563 . _:b420373596 "4"^^ . _:b420373730 . _:b420373599 "4"^^ . _:b6576679 "Dosages of RO28-2653 used in the present study were similar to those administered in pharmacodynamic studies in rat and mouse models (Kilian et al., 2006; Abramjuk et al., >>2007<<). Although nonselective MMP-blocking agents may cause severe adverse side effects (Bernardo et al., 2002), RO28-2653 did not show major side effects in rat and monkey toxicological studies (unpublished data)." . _:b420373741 . _:b420373598 "4"^^ . _:b6576681 "IL-23 has been proposed to induce pathology through the proliferation and maintenance of IL-17\u2013secreting cells (Aggarwal et al., >>2003<<; Bettelli et al., 2007). In contrast, our results demonstrate that the pathogenic role of IL-23 was independent of IL-17 but dependent on IL-22." . _:b420373740 . _:b420373593 "4"^^ . . _:b420373743 . . _:b420373592 "4"^^ . _:b420373742 . _:b420373527 . . . _:b6576676 "data, several studies have demonstrated that MMP-2 and MMP-9 are up-regulated during active episodes of IBD in humans as well as in animal models of colitis (Baugh et al., 1998; Castaneda et al., 2005; Yen et al., 2006; Gordon et al., >>2008<<), and that IL-23 is able to induce their expression (Ivanov et al., 2007)." . _:b420373595 "4"^^ . _:b420373737 . _:b420373594 "4"^^ . _:b420373736 . _:b420373730 . _:b420373605 "4"^^ . _:b420373739 . _:b420373604 "4"^^ . _:b420373779 . _:b420373738 . . _:b420373607 "4"^^ . _:b420374044 . _:b420373749 . . _:b420373855 . _:b420373870 . _:b420373606 "4"^^ . _:b420373748 . _:b420373710 . _:b6576720 . _:b420373601 "4"^^ . _:b420373751 . _:b420373635 . _:b420373600 "4"^^ . _:b420373643 . _:b420373750 . _:b420373603 "4"^^ . _:b420373745 . . _:b420373602 "4"^^ . _:b420373744 . _:b420373926 . _:b420373613 "4"^^ . _:b420373747 . _:b420373791 . _:b420373612 "4"^^ . _:b420373746 . _:b420373661 . _:b420373615 "4"^^ . _:b420373757 . _:b420373486 . . _:b420373487 . . _:b420373574 . _:b420373614 "4"^^ . _:b420373756 . _:b420373822 . _:b420373492 . _:b6576712 . _:b420373609 "4"^^ . _:b420373493 . _:b420373759 . _:b420373494 . _:b420373495 . . _:b420373488 . _:b420373937 . _:b420373489 . _:b420373608 "4"^^ . _:b420373758 . _:b6576665 "NO concentrations in supernatants were determined by Griess reaction, as previously described (Heimesaat et al., >>2006<<)." . _:b420373490 . _:b420373491 . . _:b420373500 . _:b420373611 "4"^^ . _:b420373501 . _:b420373753 . _:b420373502 . . _:b420373864 . _:b420373503 . _:b420373496 . _:b420373610 "4"^^ . _:b420373497 . _:b420373752 . _:b420373498 . _:b420373741 . _:b420373499 . . _:b420373621 "4"^^ . _:b420373755 . _:b6576686 "In agreement with our data, several studies have demonstrated that IL-17 and IL-22 possess distinct roles during immune responses (Cruz et al., 2006; Kreymborg et al., 2007; Schulz et al., 2008; Sugimoto et al., >>2008<<; Wolk et al., 2009)." . _:b420373620 "4"^^ . _:b420373754 . _:b420373979 . . _:b420373623 "4"^^ . . . _:b420373622 "4"^^ . _:b420373630 . _:b420373617 "4"^^ . _:b420373616 "4"^^ . . _:b420373619 "4"^^ . . _:b420373623 . _:b420373618 "4"^^ . _:b420373629 "4"^^ . _:b420373816 . _:b420373628 "4"^^ . _:b420373579 . . _:b420373631 "4"^^ . _:b420373964 . . . _:b420373630 "4"^^ . _:b6576672 _:b6576708 . _:b420373625 "4"^^ . _:b420373793 . _:b6576672 _:b6576709 . _:b420373775 . _:b6576672 _:b6576710 . _:b6576672 _:b6576711 . _:b6576672 _:b6576704 . _:b420373624 "4"^^ . _:b6576672 _:b6576705 . _:b6576672 _:b6576706 . _:b6576672 _:b6576707 . _:b6576672 _:b6576716 . _:b420373627 "4"^^ . _:b6576672 _:b6576717 . _:b6576672 _:b6576718 . _:b420373935 . _:b6576672 _:b6576719 . _:b6576672 _:b6576712 . _:b420373626 "4"^^ . _:b6576672 _:b6576713 . _:b420373674 . _:b6576672 _:b6576714 . _:b6576672 _:b6576715 . _:b420373637 "4"^^ . . _:b6576672 _:b6576720 . _:b420373636 "4"^^ . _:b6576672 _:b6576721 . . _:b420373639 "4"^^ . _:b420373899 . _:b420373638 "4"^^ . . _:b6576672 _:b6576676 . _:b420373633 "4"^^ . _:b6576672 _:b6576677 . _:b6576672 _:b6576678 . _:b6576672 _:b6576679 . . _:b6576672 _:b6576673 . _:b420373632 "4"^^ . _:b6576672 _:b6576674 . _:b6576672 _:b6576675 . _:b6576672 _:b6576684 . _:b420373635 "4"^^ . _:b6576672 _:b6576685 . _:b6576672 _:b6576686 . _:b6576672 _:b6576687 . _:b6576672 _:b6576680 . _:b420373634 "4"^^ . _:b6576672 _:b6576681 . _:b6576672 _:b6576682 . _:b6576672 _:b6576683 . _:b6576672 _:b6576692 . _:b420373645 "4"^^ . _:b6576672 _:b6576693 . _:b420373650 . _:b6576672 _:b6576694 . _:b6576672 _:b6576695 . _:b6576672 _:b6576688 . _:b420373644 "4"^^ . _:b6576672 _:b6576689 . _:b6576672 _:b6576690 . _:b6576672 _:b6576691 . _:b420373647 "3"^^ . . _:b6576672 _:b6576700 . _:b6576672 _:b6576701 . _:b6576672 _:b6576702 . _:b6576672 _:b6576703 . _:b420373646 "3"^^ . _:b6576672 _:b6576696 . _:b6576672 _:b6576697 . _:b6576672 _:b6576698 . _:b6576672 _:b6576699 . _:b420373641 "4"^^ . . _:b420373668 . _:b420373640 "4"^^ . _:b420373596 . _:b420373643 "4"^^ . . _:b420373642 "4"^^ . _:b420373653 "3"^^ . _:b420373652 "3"^^ . _:b420373655 "3"^^ . _:b420373654 "3"^^ . . _:b420373673 . . _:b420373649 "3"^^ . _:b6576699 "of studies have reported a rather protective role of IL-22, especially in hepatitis and colitis experimental models (Zenewicz et al., 2007; Cella et al., 2008; Satoh-Takayama et al., 2008; Sugimoto et al., 2008; Zenewicz et al., >>2008<<). In regard to intestinal inflammation, IL-22 protected mice from colitis in a CD45RBhi transfer model (Zenewicz et al., 2008), and IL-22 deficiency rendered mice susceptible to Citrobacter rodentium\u2013 and dextran sulfate sodium\u2013induced" . _:b420373648 "3"^^ . _:b420373721 . _:b420373651 "3"^^ . _:b420373821 . _:b6576669 . _:b420373650 "3"^^ . . _:b6576680 . . _:b420373717 . _:b420373661 "3"^^ . _:b420373922 . _:b6576667 _:b6576668 . _:b420373660 "3"^^ . _:b6576667 _:b6576669 . _:b420373861 . _:b6576667 _:b6576670 . _:b6576667 _:b6576671 . _:b420373663 "3"^^ . _:b6576716 . _:b420373662 "3"^^ . _:b420373657 "3"^^ . _:b6576660 _:b6576661 . . _:b6576660 _:b6576662 . _:b6576660 _:b6576663 . _:b420373656 "3"^^ . . . _:b420373659 "3"^^ . . _:b6576660 _:b6576664 . _:b420373658 "3"^^ . _:b6576660 _:b6576665 . _:b6576660 _:b6576666 . _:b420373669 "3"^^ . . . _:b420373668 "3"^^ . _:b420373671 "3"^^ . _:b420373690 . _:b6576708 . _:b420373670 "3"^^ . _:b420373665 "3"^^ . _:b420373778 . _:b420373664 "3"^^ . _:b420373667 "3"^^ . _:b420373666 "3"^^ . _:b420373677 "3"^^ . . _:b420373697 . _:b420373676 "3"^^ . _:b420373679 "3"^^ . . _:b420373678 "3"^^ . _:b420373679 . _:b420373673 "3"^^ . _:b420373672 "3"^^ . _:b420373675 "3"^^ . . _:b420373674 "3"^^ . _:b420373685 "3"^^ . _:b420373684 "3"^^ . _:b420373687 "3"^^ . _:b420373607 . _:b420373686 "3"^^ . _:b420373681 "3"^^ . _:b420373680 "3"^^ . _:b420373648 . _:b420373598 . _:b420373683 "3"^^ . _:b420373682 "3"^^ . . _:b420373693 "3"^^ . _:b420373655 . _:b420373556 . _:b420373799 . _:b420373692 "3"^^ . . _:b420373695 "3"^^ . _:b420373694 "3"^^ . _:b420373498 . _:b420373810 . _:b420373689 "3"^^ . _:b420373552 . _:b420373521 . _:b420373688 "3"^^ . _:b6576699 . _:b420373691 "3"^^ . _:b420374023 . . _:b6576688 "High concentrations of IFN-\u03B3 in the small intestine of mice might have contributed to the down-regulation of IL-17 production, as previously shown in models of adjuvant-induced arthritis (Kim et al., >>2008<<) and during mycobacterial infection (Cruz et al., 2006)." . _:b420373716 . _:b420373690 "3"^^ . . _:b420373513 . _:b6576700 . _:b420373701 "3"^^ . _:b420373700 "3"^^ . . _:b420373703 "3"^^ . . _:b420373702 "3"^^ . _:b420374002 . . _:b420373697 "3"^^ . _:b420373765 . _:b420373696 "3"^^ . _:b420374008 . _:b420373699 "3"^^ . . _:b420373698 "3"^^ . _:b420373709 "3"^^ . _:b6576706 "Neutralization of IL-22 has recently been reported to block CXCL-8 expression by intestinal epithelial cells after stimulation with T memory cells (Kleinschek et al., >>2009<<). Lastly, pathogenic IL-22\u2013producing cells might constitute a subpopulation of cells, different from Th17 and NK22 cells. IL-22 production is higher in Th1 cells than in Th17 cells (Volpe et al., 2008), and a unique IL-22\u2013producing" . _:b420373708 "3"^^ . _:b420373711 "3"^^ . . . _:b420373710 "3"^^ . _:b420373663 . _:b420373705 "3"^^ . _:b420373704 "3"^^ . _:b420373707 "3"^^ . _:b420373613 . _:b6576709 "al., 2008), and a unique IL-22\u2013producing population of NKp46+ROR\u03B3t+ natural killer cells, termed NK22 cells, was identified in the dermis, lamina propria, and other mucosa-associated lymphoid tissues (Cella et al., 2008; Luci et al., >>2008<<; Sanos et al., 2009; Satoh-Takayama et al., 2008; Zenewicz et al., 2008). Furthermore, a human Th cell population that secretes IL-22 but not IL-17 nor IFN-\u03B3 has been recently reported (Duhen et al., 2009; Trifari et al., 2009)." . _:b420373639 . _:b6576696 . _:b420373706 "3"^^ . _:b420373891 . _:b420373717 "3"^^ . _:b6576668 "We have previously demonstrated that peroral infection of susceptible C57BL/6 mice with 100 cysts of T. gondii ME49 leads to Th1-type small intestinal necrosis (panileitis; Liesenfeld et al., >>1996<<). To investigate the role of IL-23 in the development of ileal immunopathology, IL-23p19\u2212/\u2212 mice were infected orally." . . . _:b420373716 "3"^^ . _:b420373719 "3"^^ . _:b420373718 "3"^^ . _:b420373770 . _:b420373713 "3"^^ . _:b420373712 "3"^^ . . _:b420373715 "3"^^ . _:b420373913 . _:b420373714 "3"^^ . . _:b420373725 "3"^^ . _:b420373724 "3"^^ . . _:b420373727 "3"^^ . _:b420373683 . _:b420373726 "3"^^ . _:b420373721 "3"^^ . _:b420373780 . _:b420373720 "3"^^ . . _:b420373571 . _:b420373723 "3"^^ . _:b420373722 "3"^^ . . . _:b420373733 "3"^^ . _:b420373732 "3"^^ . _:b420373824 . _:b420373735 "2"^^ . _:b420374017 . _:b420373734 "3"^^ . _:b420373620 . _:b420373729 "3"^^ . _:b420373728 "3"^^ . _:b420373908 . . _:b420373731 "3"^^ . _:b420373730 "3"^^ . . . _:b420373741 "2"^^ . _:b420373740 "2"^^ . _:b420373743 "2"^^ . _:b420373742 "2"^^ . _:b420373737 "2"^^ . . _:b420373736 "2"^^ . . _:b420373739 "2"^^ . . _:b420373815 . _:b420373738 "2"^^ . . _:b420373740 . _:b420373749 "2"^^ . _:b420374020 . _:b420374021 . _:b420374022 . _:b420373748 "2"^^ . _:b420374023 . _:b420374016 . _:b420374017 . _:b420374018 . _:b420373839 . _:b420374019 . _:b420373751 "2"^^ . . _:b420374028 . _:b420374029 . _:b420374030 . _:b420373750 "2"^^ . _:b420374031 . _:b420374024 . _:b420374025 . _:b420374026 . _:b420373745 "2"^^ . _:b420374027 . _:b420374036 . . _:b420374037 . _:b420374038 . _:b420373744 "2"^^ . _:b420374039 . . _:b420374032 . _:b420374033 . . _:b420374034 . _:b420373747 "2"^^ . _:b420373924 . _:b420374035 . _:b420374044 . _:b420374045 . . _:b420374046 . _:b420373746 "2"^^ . _:b420374047 . _:b420374040 . _:b420374041 . _:b420374042 . _:b420373757 "2"^^ . _:b420374043 . _:b420374052 . _:b6576675 . _:b420374053 . . _:b420374054 . _:b420373756 "2"^^ . _:b420374055 . _:b420374048 . _:b420374049 . . _:b420374050 . _:b420373759 "2"^^ . _:b420374051 . _:b420373758 "2"^^ . _:b420374056 . _:b420374057 . _:b420373605 . _:b420374058 . _:b420373753 "2"^^ . _:b420373752 "2"^^ . _:b420373970 . _:b420373755 "2"^^ . _:b6576671 . _:b420374040 . _:b420373754 "2"^^ . _:b420373765 "2"^^ . _:b420373662 . . _:b420373764 "2"^^ . _:b420373554 . _:b420373767 "2"^^ . _:b420373766 "2"^^ . _:b420373761 "2"^^ . . . _:b420373981 . _:b420373760 "2"^^ . . _:b420374030 . _:b420373763 "2"^^ . . . _:b420373762 "2"^^ . . _:b420373806 . _:b420373773 "2"^^ . . _:b420373772 "2"^^ . _:b420373676 . _:b420373775 "2"^^ . _:b420373774 "2"^^ . . _:b420373769 "2"^^ . _:b420373604 . . _:b420373768 "2"^^ . . _:b420373771 "2"^^ . _:b420373956 . . _:b420373770 "2"^^ . _:b420373781 "2"^^ . _:b420373780 "2"^^ . _:b420373783 "2"^^ . _:b420373782 "2"^^ . _:b420373624 . _:b420373610 . _:b420373777 "2"^^ . . _:b420373776 "2"^^ . . _:b420373813 . _:b420373779 "2"^^ . _:b420373778 "2"^^ . . _:b420373789 "2"^^ . _:b420373978 . _:b420373788 "2"^^ . . _:b420373791 "2"^^ . _:b420373790 "2"^^ . _:b6576689 "of IFN-\u03B3 in the small intestine of mice might have contributed to the down-regulation of IL-17 production, as previously shown in models of adjuvant-induced arthritis (Kim et al., 2008) and during mycobacterial infection (Cruz et al., >>2006<<)." . _:b420373785 "2"^^ . _:b420373784 "2"^^ . _:b420373787 "2"^^ . . _:b420373786 "2"^^ . _:b420373797 "2"^^ . _:b420373704 . _:b420373988 . _:b420373796 "2"^^ . . _:b420373799 "2"^^ . _:b420373826 . _:b420373798 "2"^^ . _:b420373949 . _:b420373793 "2"^^ . _:b420373792 "2"^^ . _:b420373940 . . _:b420373795 "2"^^ . _:b420373608 . _:b420373794 "2"^^ . _:b420373802 . _:b420373805 "2"^^ . . _:b420373654 . _:b420373804 "2"^^ . . _:b420373737 . . _:b420373817 . _:b420373767 . _:b420373807 "2"^^ . . _:b420373806 "2"^^ . _:b420373726 . _:b420373801 "2"^^ . . _:b420373800 "2"^^ . . _:b420373518 . _:b420373803 "2"^^ . . _:b420373802 "2"^^ . _:b420373813 "2"^^ . _:b420373857 . _:b420373812 "2"^^ . . _:b420373975 . _:b420373815 "2"^^ . _:b420373814 "2"^^ . _:b6576704 . . . _:b420373961 . _:b420373809 "2"^^ . . _:b420373808 "2"^^ . . . _:b420373811 "2"^^ . . _:b420373850 . _:b420373810 "2"^^ . _:b420373811 . _:b420373821 "2"^^ . . _:b420373820 "2"^^ . . _:b420373823 "2"^^ . . _:b420373822 "2"^^ . _:b420373578 . . _:b420373817 "2"^^ . _:b420373816 "2"^^ . . _:b420373819 "2"^^ . _:b420373881 . _:b420373818 "2"^^ . _:b420373829 "2"^^ . _:b420373828 "2"^^ . _:b420373622 . _:b420373831 "2"^^ . _:b420373708 . _:b420373830 "2"^^ . . _:b6576679 . _:b420373825 "2"^^ . _:b420373766 . _:b420373824 "2"^^ . . _:b420373827 "2"^^ . _:b420373782 . _:b420373764 . . _:b420373826 "2"^^ . . _:b420373837 "2"^^ . _:b420373836 "2"^^ . . _:b420373839 "2"^^ . _:b420373838 "2"^^ . _:b420373833 "2"^^ . _:b420373631 . _:b420373832 "2"^^ . . . _:b420373835 "2"^^ . . _:b420373528 . _:b420373834 "2"^^ . . _:b420373948 . . _:b420373845 "2"^^ . . _:b420373844 "2"^^ . . _:b420373847 "2"^^ . _:b6576674 . _:b420373713 . _:b420373846 "2"^^ . _:b420373841 "2"^^ . _:b420373874 . _:b420373848 . _:b420373840 "2"^^ . . _:b420373843 "2"^^ . _:b420373934 . . _:b420373842 "2"^^ . _:b420373884 . _:b420373853 "2"^^ . . _:b420373852 "2"^^ . _:b420373855 "2"^^ . _:b420374041 . . _:b420373854 "2"^^ . . _:b420373614 . _:b420373849 "2"^^ . . _:b420373487 . _:b420373848 "2"^^ . . _:b420373486 . _:b420373851 "2"^^ . _:b420373850 "2"^^ . _:b420373861 "2"^^ . _:b420373877 . _:b420373637 . _:b420373860 "2"^^ . _:b420373789 . _:b420373500 . _:b420373589 . _:b420373863 "2"^^ . _:b420373493 . _:b420373862 "2"^^ . . _:b420373492 . _:b420373989 . _:b420373857 "2"^^ . _:b420373733 . _:b6576685 . _:b420373495 . _:b420373856 "2"^^ . _:b420373494 . . . _:b420373859 "2"^^ . _:b6576713 "Furthermore, a human Th cell population that secretes IL-22 but not IL-17 nor IFN-\u03B3 has been recently reported (Duhen et al., >>2009<<; Trifari et al., 2009)." . _:b420373489 . _:b420373858 "2"^^ . . _:b420373488 . _:b420373869 "2"^^ . . _:b420373491 . _:b420373868 "2"^^ . _:b420373490 . _:b420373871 "2"^^ . . _:b420373501 . _:b420373870 "2"^^ . _:b420373999 . _:b420373500 . . _:b420373865 "2"^^ . _:b420373503 . _:b420373864 "2"^^ . . _:b420374015 . _:b420373502 . _:b420373867 "2"^^ . _:b420373497 . _:b420373769 . _:b420373866 "2"^^ . _:b420373768 . . _:b420373496 . _:b420373877 "2"^^ . _:b420373508 . _:b420373509 . _:b420373510 . _:b420373499 . _:b420373876 "2"^^ . _:b420373511 . _:b420373504 . _:b420373505 . _:b420373506 . _:b420373498 . _:b420373879 "2"^^ . _:b420373507 . _:b420373516 . _:b420373517 . _:b420373518 . _:b420373878 "2"^^ . _:b420373519 . _:b420373512 . _:b420373513 . _:b420373514 . _:b420373873 "2"^^ . _:b420373515 . _:b420373524 . _:b420373525 . _:b420373526 . _:b420373872 "2"^^ . _:b420373527 . _:b420373520 . _:b420373962 . _:b420373521 . . . _:b420373522 . _:b420373875 "2"^^ . _:b420373523 . _:b420373487 . _:b420373532 . _:b420373530 . _:b420373533 . _:b6576716 "However, flow cytometry did not associate IL-22 production with NK cells, as recently described (Cella et al., >>2008<<; Luci et al., 2008; Sanos et al., 2009; Satoh-Takayama et al., 2008; Zenewicz et al., 2008)." . _:b420373534 . _:b420373874 "2"^^ . _:b420373535 . _:b420373528 . _:b420373529 . _:b420373530 . _:b420373885 "2"^^ . _:b420373531 . _:b420373540 . _:b420373541 . _:b420373801 . _:b420373542 . . _:b420373884 "2"^^ . _:b420373543 . _:b420373536 . . . _:b420373537 . _:b420373538 . _:b420373887 "2"^^ . _:b420373539 . _:b420373548 . _:b420373549 . _:b420373550 . _:b420373886 "2"^^ . _:b420373551 . _:b420373544 . _:b420373545 . _:b420373546 . _:b420373881 "2"^^ . _:b420373547 . _:b420373556 . _:b420373557 . _:b420373558 . _:b420373880 "2"^^ . _:b420373559 . _:b420373552 . _:b420373553 . _:b420373554 . _:b420373883 "2"^^ . . _:b420373555 . _:b420373564 . _:b420373565 . _:b420373566 . _:b420373882 "2"^^ . . _:b420373567 . _:b420373560 . _:b420373561 . _:b420373562 . _:b420373805 . _:b420373893 "2"^^ . . _:b420373563 . _:b420373572 . _:b420373573 . _:b420373574 . _:b420373892 "2"^^ . _:b420373575 . _:b420373568 . _:b420373569 . _:b420373570 . _:b420373895 "2"^^ . _:b420373571 . _:b420373580 . _:b420373581 . _:b420373736 . _:b420373582 . _:b420373894 "2"^^ . _:b420373583 . _:b420373576 . _:b420373577 . _:b420373578 . _:b420373889 "2"^^ . _:b420373723 . _:b420373579 . _:b420373588 . _:b420373589 . _:b420373590 . _:b420373888 "2"^^ . _:b420373959 . _:b420373591 . _:b420373584 . . _:b420373585 . _:b420373609 . _:b420373586 . _:b420373891 "2"^^ . _:b420373587 . _:b420373596 . _:b6576704 "Furthermore, IL-22 induces the expression of antimicrobial peptides in epithelial cells (Liang et al., 2006; Aujla et al., >>2007<<; Zheng et al., 2008)." . _:b420373597 . _:b420373598 . _:b420373890 "2"^^ . _:b420373555 . _:b420373599 . _:b420373592 . _:b420373593 . _:b420373594 . _:b420373901 "2"^^ . _:b420373595 . _:b420373604 . _:b420374058 . _:b420373605 . _:b420373606 . _:b420373900 "2"^^ . . _:b420373607 . _:b420373600 . _:b420373601 . _:b420373602 . _:b420373903 "2"^^ . _:b420373603 . _:b420373612 . _:b420373613 . _:b420373614 . _:b420373902 "2"^^ . _:b420373615 . _:b420373608 . _:b420373609 . _:b420373610 . _:b420373897 "2"^^ . _:b420373611 . . _:b420373620 . _:b420373621 . _:b420373622 . _:b420373896 "2"^^ . _:b420373623 . _:b420373616 . _:b420373617 . _:b420373618 . . _:b420373619 . _:b420373899 "2"^^ . _:b420373628 . _:b420373629 . _:b420373630 . _:b420373898 "2"^^ . _:b420373631 . _:b420373624 . _:b420373625 . _:b420373626 . _:b420373909 "2"^^ . _:b420373634 . _:b420373627 . _:b420373636 . _:b420373637 . _:b420373638 . _:b420373908 "2"^^ . _:b420373639 . _:b420373632 . _:b420373633 . . _:b420373634 . _:b420373911 "2"^^ . _:b420373635 . _:b420373644 . _:b420373645 . _:b420373646 . . _:b420373910 "2"^^ . _:b420373647 . _:b420373640 . _:b420373641 . _:b420373642 . _:b420373905 "2"^^ . _:b420373643 . _:b420373652 . _:b420373653 . _:b420373654 . _:b420373904 "2"^^ . _:b420373655 . _:b420373648 . _:b420373649 . _:b420373650 . _:b6576682 . _:b420373907 "2"^^ . . _:b420373651 . _:b420373660 . _:b420374009 . _:b420373661 . _:b420373662 . _:b420373906 "2"^^ . _:b420373663 . _:b420373656 . _:b420373657 . _:b420373658 . _:b420373917 "2"^^ . _:b420373659 . _:b420373668 . _:b6576696 "Zheng et al., 2007; Ma et al., 2008; Wolk et al., 2009), an increasing number of studies have reported a rather protective role of IL-22, especially in hepatitis and colitis experimental models (Zenewicz et al., 2007; Cella et al., >>2008<<; Satoh-Takayama et al., 2008; Sugimoto et al., 2008; Zenewicz et al., 2008)." . _:b420373669 . _:b420373670 . _:b420373916 "2"^^ . _:b420373671 . _:b420373664 . _:b420373665 . _:b420373666 . _:b420373919 "2"^^ . . _:b420373667 . _:b420373676 . _:b420373677 . _:b420373678 . _:b420373918 "2"^^ . _:b420373679 . _:b420373672 . _:b420373673 . _:b420373674 . _:b420373913 "2"^^ . _:b420373675 . _:b420373684 . _:b420373685 . _:b420373686 . _:b420373912 "2"^^ . _:b420373687 . _:b420373680 . _:b420373681 . _:b420373682 . _:b420373915 "2"^^ . _:b420373683 . _:b420373692 . _:b420373693 . _:b420373694 . _:b420373914 "2"^^ . _:b420373695 . _:b420373688 . _:b420373689 . _:b420373690 . _:b6576673 "In accordance with our data, several studies have demonstrated that MMP-2 and MMP-9 are up-regulated during active episodes of IBD in humans as well as in animal models of colitis (Baugh et al., >>1998<<; Castaneda et al., 2005; Yen et al., 2006; Gordon et al., 2008), and that IL-23 is able to induce their expression (Ivanov et al., 2007)." . _:b420373925 "2"^^ . _:b420373691 . _:b420373700 . _:b420373701 . . _:b420373702 . _:b420373520 . _:b420373924 "2"^^ . _:b420373808 . _:b420373703 . _:b420373696 . _:b6576711 "of NKp46+ROR\u03B3t+ natural killer cells, termed NK22 cells, was identified in the dermis, lamina propria, and other mucosa-associated lymphoid tissues (Cella et al., 2008; Luci et al., 2008; Sanos et al., 2009; Satoh-Takayama et al., >>2008<<; Zenewicz et al., 2008). Furthermore, a human Th cell population that secretes IL-22 but not IL-17 nor IFN-\u03B3 has been recently reported (Duhen et al., 2009; Trifari et al., 2009)." . _:b420373697 . _:b420373698 . _:b420373927 "2"^^ . _:b420373699 . _:b420373708 . _:b420373709 . _:b420373710 . _:b420373592 . _:b420373926 "2"^^ . _:b420373711 . . _:b420373704 . _:b420373705 . _:b420373706 . _:b420373921 "2"^^ . _:b420373707 . _:b420373716 . _:b420373717 . . _:b420373718 . _:b420373920 "2"^^ . _:b6576674 "In accordance with our data, several studies have demonstrated that MMP-2 and MMP-9 are up-regulated during active episodes of IBD in humans as well as in animal models of colitis (Baugh et al., 1998; Castaneda et al., >>2005<<; Yen et al., 2006; Gordon et al., 2008), and that IL-23 is able to induce their expression (Ivanov et al., 2007)." . . _:b420373719 . . _:b420373712 . _:b420373713 . _:b420373714 . _:b420373923 "2"^^ . _:b420373930 . _:b420373715 . _:b420373955 . _:b420373724 . _:b420373725 . _:b420373880 . _:b420373726 . _:b420373922 "2"^^ . _:b420373727 . _:b420373720 . _:b420373721 . _:b420373722 . _:b420373933 "2"^^ . _:b420373723 . _:b420373732 . _:b420373733 . . _:b420373734 . _:b420373925 . _:b420373932 "2"^^ . _:b420373735 . _:b420373728 . _:b420373729 . _:b420373488 . _:b420373730 . _:b420373935 "2"^^ . _:b420373731 . _:b420373740 . _:b420373741 . _:b420373742 . _:b420373934 "2"^^ . _:b420373743 . _:b420373736 . _:b420373737 . _:b420373738 . _:b420373929 "2"^^ . _:b420373739 . _:b420373748 . _:b420373749 . _:b420373575 . _:b420373750 . _:b420373928 "2"^^ . _:b420373751 . _:b420373844 . _:b420373744 . . _:b420373745 . . _:b420373746 . _:b420373931 "2"^^ . _:b420373747 . _:b420373756 . _:b420373757 . _:b420373758 . _:b420373930 "2"^^ . _:b420373759 . _:b420373752 . _:b420373753 . _:b420373754 . _:b420373941 "2"^^ . _:b420373755 . _:b420373764 . _:b420373765 . _:b420373766 . _:b420373940 "2"^^ . _:b420373767 . _:b420373760 . _:b420373761 . _:b420373762 . _:b420373943 "2"^^ . _:b420373763 . _:b420373772 . _:b420373677 . _:b420373773 . _:b420373774 . _:b420373942 "2"^^ . . _:b420373775 . _:b420373768 . _:b420373769 . _:b420373770 . _:b420373937 "2"^^ . _:b420373771 . _:b420373780 . _:b420373781 . _:b420373782 . _:b420373936 "2"^^ . _:b420373783 . _:b420373776 . . _:b420373777 . _:b420373778 . _:b420373939 "2"^^ . . _:b420373779 . _:b420373788 . _:b420373789 . . _:b420373790 . _:b420373938 "2"^^ . _:b420373791 . _:b420373784 . _:b420373537 . _:b420373785 . _:b420373536 . _:b420373786 . _:b420373949 "2"^^ . _:b420373787 . _:b420373796 . _:b420373797 . _:b420373798 . _:b420373948 "2"^^ . _:b420373799 . _:b420373792 . _:b420373793 . _:b420373794 . _:b420373951 "2"^^ . _:b420373828 . _:b420373795 . _:b420373804 . _:b420373805 . _:b420373806 . _:b6576701 "IL-22 protected mice from colitis in a CD45RBhi transfer model (Zenewicz et al., 2008), and IL-22 deficiency rendered mice susceptible to Citrobacter rodentium\u2013 and dextran sulfate sodium\u2013induced colitis (Satoh-Takayama et al., >>2008<<; Zheng et al., 2008). Furthermore, IL-22 induces the expression of antimicrobial peptides in epithelial cells (Liang et al., 2006; Aujla et al., 2007; Zheng et al., 2008)." . _:b420373950 "2"^^ . _:b420373807 . _:b420373800 . _:b420373801 . . _:b420373802 . _:b420373945 "2"^^ . _:b420373803 . _:b420373812 . _:b420373813 . _:b420373814 . _:b420373776 . _:b420373944 "2"^^ . _:b420373815 . _:b420374055 . _:b420373808 . _:b420373809 . _:b420373810 . _:b420373947 "2"^^ . _:b420373811 . _:b420373820 . _:b420373821 . _:b420373822 . _:b6576710 "IL-22\u2013producing population of NKp46+ROR\u03B3t+ natural killer cells, termed NK22 cells, was identified in the dermis, lamina propria, and other mucosa-associated lymphoid tissues (Cella et al., 2008; Luci et al., 2008; Sanos et al., >>2009<<; Satoh-Takayama et al., 2008; Zenewicz et al., 2008). Furthermore, a human Th cell population that secretes IL-22 but not IL-17 nor IFN-\u03B3 has been recently reported (Duhen et al., 2009; Trifari et al., 2009)." . _:b420373946 "2"^^ . _:b420373823 . _:b420373816 . _:b420373817 . _:b420373892 . _:b420373818 . . _:b420373819 . _:b420373957 "2"^^ . _:b420373828 . . _:b420373829 . _:b420373830 . _:b420373956 "2"^^ . _:b420373831 . _:b420373824 . _:b420373825 . _:b420373826 . _:b420373959 "2"^^ . _:b420373827 . _:b420373836 . . _:b6576685 "In agreement with our data, several studies have demonstrated that IL-17 and IL-22 possess distinct roles during immune responses (Cruz et al., 2006; Kreymborg et al., 2007; Schulz et al., >>2008<<; Sugimoto et al., 2008; Wolk et al., 2009)." . _:b420373837 . _:b420373838 . _:b420373958 "2"^^ . _:b420373839 . . _:b420373832 . _:b420373833 . _:b420373834 . _:b420373953 "2"^^ . _:b420373835 . _:b420373844 . _:b420373845 . _:b420373846 . _:b420373952 "2"^^ . . _:b420373847 . _:b420373840 . _:b420373841 . _:b420373842 . _:b420373955 "2"^^ . _:b420373843 . _:b420373852 . _:b420373853 . _:b420373854 . _:b420373954 "2"^^ . _:b420373855 . _:b420373848 . _:b420373849 . . _:b420373850 . _:b420373965 "2"^^ . _:b420373851 . _:b420373860 . _:b420373982 . _:b420373861 . _:b420373862 . _:b420373964 "2"^^ . _:b420373863 . _:b420373856 . _:b420373857 . _:b420373858 . _:b420373967 "2"^^ . _:b420373859 . _:b420373868 . . _:b420373869 . . . _:b420373870 . _:b420373966 "2"^^ . _:b420373871 . _:b420373864 . _:b420373865 . _:b420373866 . _:b420373856 . _:b420373961 "2"^^ . _:b420373867 . _:b420373876 . _:b420373877 . _:b420373878 . _:b420373960 "2"^^ . . _:b420373618 . _:b420373879 . _:b420373872 . _:b420373873 . _:b420373874 . _:b420373963 "2"^^ . _:b6576687 "In agreement with our data, several studies have demonstrated that IL-17 and IL-22 possess distinct roles during immune responses (Cruz et al., 2006; Kreymborg et al., 2007; Schulz et al., 2008; Sugimoto et al., 2008; Wolk et al., >>2009<<). Moreover, our study provides strong evidence that IL-22 and IL-17 are inversely regulated in ileitis." . _:b420373875 . _:b420373884 . _:b420373885 . _:b420373886 . _:b420373573 . _:b420373962 "2"^^ . _:b6576721 "In agreement with a previous study, IL-22 production was also dependent on the presence of the normal gut flora, because gnotobiotic mice displayed significantly lower IL-22 concentrations (Satoh-Takayama et al., >>2008<<)." . _:b420373887 . _:b420373880 . _:b420373881 . _:b420373882 . _:b420373973 "2"^^ . _:b420373883 . _:b420373892 . _:b420373893 . _:b420373894 . _:b420373972 "2"^^ . _:b420373895 . _:b420373888 . _:b420373889 . _:b420373890 . _:b420373975 "2"^^ . _:b420373891 . _:b420373900 . _:b420373901 . . _:b420373902 . . _:b420373903 . _:b420373974 "2"^^ . . _:b420373936 . _:b420373896 . _:b420373897 . _:b420373898 . _:b420373969 "2"^^ . _:b420373899 . _:b420373908 . _:b420373909 . . _:b420373910 . _:b420373968 "2"^^ . . _:b420373911 . _:b420373904 . _:b420373905 . _:b420373906 . _:b420373971 "2"^^ . _:b420373907 . _:b420373916 . _:b420373917 . _:b420373684 . _:b420373918 . _:b420373970 "2"^^ . _:b420373919 . . _:b420373912 . _:b420373913 . _:b420373914 . _:b420373981 "2"^^ . _:b420373915 . _:b420373924 . _:b420373925 . _:b420373926 . _:b420373980 "2"^^ . _:b420373927 . _:b420373920 . _:b420373921 . . . _:b420373922 . _:b420373983 "2"^^ . _:b420373923 . _:b420373932 . _:b420373933 . _:b420373934 . _:b420373982 "2"^^ . _:b420373935 . _:b420373928 . . _:b420373929 . _:b420373930 . _:b420373977 "2"^^ . _:b420373931 . . _:b420373940 . _:b420373941 . _:b420373942 . _:b420373976 "2"^^ . _:b420373943 . _:b420373936 . _:b420373937 . _:b420373938 . _:b420373979 "2"^^ . _:b420373939 . . _:b420373948 . . _:b420373949 . _:b420373950 . _:b420373978 "2"^^ . _:b420373951 . _:b420373944 . _:b420373945 . . _:b420373946 . _:b420373989 "2"^^ . _:b420373947 . _:b420373956 . _:b420373957 . _:b420373515 . _:b420373958 . _:b420373988 "2"^^ . _:b420373959 . _:b420373952 . . _:b420373953 . _:b420373954 . _:b420373851 . _:b420373991 "2"^^ . _:b420373955 . _:b420373964 . _:b420373965 . _:b420373969 . _:b420373966 . _:b420373990 "2"^^ . _:b420373967 . _:b420373960 . _:b420373961 . . _:b420374033 . _:b420373962 . _:b420373985 "2"^^ . _:b420373963 . _:b420373972 . _:b420373973 . _:b420373974 . _:b420373984 "2"^^ . _:b420373595 . _:b420373975 . _:b420373968 . _:b420373969 . _:b420373970 . _:b420373987 "2"^^ . _:b420373971 . . _:b420373980 . _:b420373660 . _:b420373981 . _:b420373982 . _:b420373986 "2"^^ . _:b420373983 . . _:b420373976 . _:b420373977 . _:b420373978 . _:b420373714 . _:b420373979 . _:b420373997 "2"^^ . . _:b420373988 . . _:b420373989 . _:b420373990 . _:b420373996 "2"^^ . _:b420373991 . _:b420373984 . _:b420373985 . _:b420373986 . . _:b420373999 "2"^^ . _:b420373987 . _:b420373996 . . _:b420373997 . . _:b420373783 . _:b420373998 . _:b420373998 "2"^^ . _:b420373999 . _:b420373992 . _:b420373993 . _:b420373994 . _:b420373993 "2"^^ . _:b420373995 . _:b420374004 . _:b420374005 . _:b420374006 . _:b420373992 "2"^^ . . _:b420374007 . _:b420374000 . _:b420374001 . _:b420374002 . _:b420373995 "2"^^ . _:b420373519 . _:b420374003 . _:b420374012 . _:b420374013 . _:b420374014 . _:b420373974 . _:b420373994 "2"^^ . _:b420374015 . _:b420374008 . _:b420374009 . _:b420374010 . _:b420374005 "2"^^ . . _:b420374011 . . . _:b420374004 "2"^^ . _:b420374007 "2"^^ . _:b420373785 . . _:b420374006 "2"^^ . . _:b420373562 . _:b420374001 "2"^^ . _:b420374000 "2"^^ . _:b420374003 "2"^^ . . _:b420374002 "2"^^ . _:b420374013 "2"^^ . _:b420373990 . . _:b420374012 "2"^^ . _:b420373545 . _:b420373553 . _:b420374015 "2"^^ . _:b420373503 . _:b420374024 . _:b420374014 "2"^^ . _:b420374036 . _:b420374009 "2"^^ . _:b420373675 . _:b420374008 "2"^^ . . _:b420374011 "2"^^ . _:b420374010 "2"^^ . _:b420373754 . _:b420373917 . . _:b420373538 . . . . _:b420373946 . . . _:b420373687 . . . . . _:b420373722 . . _:b420373692 . . _:b420374020 . . _:b420373957 . . _:b420373665 . _:b420373831 . _:b420373985 . _:b420373750 . . . _:b420373997 . _:b420373590 . . _:b420374014 . . _:b420373490 . . . _:b6576664 . . . . _:b420373502 . . . . _:b6576703 "Furthermore, IL-22 induces the expression of antimicrobial peptides in epithelial cells (Liang et al., >>2006<<; Aujla et al., 2007; Zheng et al., 2008)." . _:b420373950 . _:b420373691 . . . _:b420373603 . _:b420373601 . . . . . . . . _:b6576682 "IL-23 has been proposed to induce pathology through the proliferation and maintenance of IL-17\u2013secreting cells (Aggarwal et al., 2003; Bettelli et al., >>2007<<). In contrast, our results demonstrate that the pathogenic role of IL-23 was independent of IL-17 but dependent on IL-22." . _:b420373492 . . _:b420373497 . _:b420373995 . . _:b6576712 "killer cells, termed NK22 cells, was identified in the dermis, lamina propria, and other mucosa-associated lymphoid tissues (Cella et al., 2008; Luci et al., 2008; Sanos et al., 2009; Satoh-Takayama et al., 2008; Zenewicz et al., >>2008<<). Furthermore, a human Th cell population that secretes IL-22 but not IL-17 nor IFN-\u03B3 has been recently reported (Duhen et al., 2009; Trifari et al., 2009)." . . .