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_:vb454429675 _:vb454429676 _:vb454429677 _:vb454429678 _:vb454429679 _:vb454429648 _:vb454429649 _:vb454429650 _:vb454429651 _:vb454429652 _:vb454429653 _:vb454429654 _:vb454429655 _:vb454429656 _:vb454429657 _:vb454429658 _:vb454429659 _:vb454429660 _:vb454429661 _:vb454429662 _:vb454429663 _:vb454429632 _:vb454429633 _:vb454429634 _:vb454429635 _:vb454429636 _:vb454429637 _:vb454429638 _:vb454429639 _:vb454429640 _:vb454429641 _:vb454429642 _:vb454429643 _:vb454429644 _:vb454429645 _:vb454429646 _:vb454429647 _:vb454429616 _:vb454429617 _:vb454429618 _:vb454429619 _:vb454429620 _:vb454429621 _:vb454429622 _:vb454429623 _:vb454429624 _:vb454429625 _:vb454429626 _:vb454429627 _:vb454429628 _:vb454429629 _:vb454429630 _:vb454429631 _:vb454429600 _:vb454429601 _:vb454429602 _:vb454429603 _:vb454429604 _:vb454429605 _:vb454429606 _:vb454429607 _:vb454429608 _:vb454429609 _:vb454429610 _:vb454429611 _:vb454429612 _:vb454429613 _:vb454429614 _:vb454429615 _:vb454429584 _:vb454429585 _:vb454429586 _:vb454429587 _:vb454429588 _:vb454429589 _:vb454429590 _:vb454429591 _:vb454429592 _:vb454429593 _:vb454429594 _:vb454429595 _:vb454429596 _:vb454429597 _:vb454429598 _:vb454429599 _:vb454429568 _:vb454429569 _:vb454429570 _:vb454429571 _:vb454429572 _:vb454429573 _:vb454429574 _:vb454429575 _:vb454429576 _:vb454429577 _:vb454429578 _:vb454429579 _:vb454429580 _:vb454429581 _:vb454429582 _:vb454429583 _:vb454429808 _:vb454429809 _:vb454429810 _:vb454429811 _:vb454429812 _:vb454429813 _:vb454429814 _:vb454429815 _:vb454429816 _:vb454429817 _:vb454429818 _:vb454429819 _:vb454429820 _:vb454429821 _:vb454429822 _:vb454429823 _:vb454429792 _:vb454429793 _:vb454429794 _:vb454429795 _:vb454429796 _:vb454429797 _:vb454429798 _:vb454429799 _:vb454429800 _:vb454429801 _:vb454429802 _:vb454429803 _:vb454429804 _:vb454429805 _:vb454429806 _:vb454429807 _:vb454429776 _:vb454429777 _:vb454429778 _:vb454429779 _:vb454429780 _:vb454429781 _:vb454429782 _:vb454429783 _:vb454429784 _:vb454429785 _:vb454429786 _:vb454429787 _:vb454429788 _:vb454429789 _:vb454429790 _:vb454429791 _:vb454429760 _:vb454429761 _:vb454429762 _:vb454429763 _:vb454429764 _:vb454429765 _:vb454429766 _:vb454429767 _:vb454429768 _:vb454429769 _:vb454429770 _:vb454429771 _:vb454429772 _:vb454429773 _:vb454429774 _:vb454429775 _:vb454429744 _:vb454429745 _:vb454429746 _:vb454429747 _:vb454429748 _:vb454429749 _:vb454429750 _:vb454429751 _:vb454429752 _:vb454429753 _:vb454429754 _:vb454429755 _:vb454429756 _:vb454429757 _:vb454429758 _:vb454429759 _:vb454429728 _:vb454429729 _:vb454429730 _:vb454429731 _:vb454429732 _:vb454429733 _:vb454429734 _:vb454429735 _:vb454429736 _:vb454429737 _:vb454429738 _:vb454429739 _:vb454429740 _:vb454429741 _:vb454429742 _:vb454429743 _:vb454429712 _:vb454429713 _:vb454429714 _:vb454429715 _:vb454429716 _:vb454429717 _:vb454429718 _:vb454429719 _:vb454429720 _:vb454429721 _:vb454429722 _:vb454429723 _:vb454429724 _:vb454429725 _:vb454429726 _:vb454429727 _:vb454429696 _:vb454429697 _:vb454429698 _:vb454429699 _:vb454429700 _:vb454429701 _:vb454429702 _:vb454429703 _:vb454429704 _:vb454429705 _:vb454429706 _:vb454429707 _:vb454429708 _:vb454429709 _:vb454429710 _:vb454429711 _:vb454429824
n2:pmcid: PMC0
bibo:doi: 10.1084%2Fjem.20102327
n4:contains: _:vb10081301 _:vb10081311 _:vb10081335

Subject Item: _:vb10081301
rdf:type: n4:Section
dc:title: materials and methods
n4:contains: _:vb10081302 _:vb10081303 _:vb10081304 _:vb10081305 _:vb10081306 _:vb10081307 _:vb10081308 _:vb10081309 _:vb10081310

Subject Item: _:vb10081302
rdf:type: n2:Context
rdf:value: Ccr7-deficient mice (Förster et al., >>1999<<), Mx-Cre x Cxcr4flox/flox mice (Sugiyama et al., 2006), and plt/plt mice (Nakano et al., 1998), as well as OT-I and OT-II TCR-transgenic and RIP-mOVA–transgenic mice (Kurts et al., 1996; Barnden et al., 1998), were described previously.
n2:mentions: n3:10520991

Subject Item: _:vb10081303
rdf:type: n2:Context
rdf:value: Ccr7-deficient mice (Förster et al., 1999), Mx-Cre x Cxcr4flox/flox mice (Sugiyama et al., >>2006<<), and plt/plt mice (Nakano et al., 1998), as well as OT-I and OT-II TCR-transgenic and RIP-mOVA–transgenic mice (Kurts et al., 1996; Barnden et al., 1998), were described previously.
n2:mentions: n3:17174120

Subject Item: _:vb10081304
rdf:type: n2:Context
rdf:value: Ccr7-deficient mice (Förster et al., 1999), Mx-Cre x Cxcr4flox/flox mice (Sugiyama et al., 2006), and plt/plt mice (Nakano et al., >>1998<<), as well as OT-I and OT-II TCR-transgenic and RIP-mOVA–transgenic mice (Kurts et al., 1996; Barnden et al., 1998), were described previously.
n2:mentions: n3:9531599

Subject Item: _:vb10081305
rdf:type: n2:Context
rdf:value: Ccr7-deficient mice (Förster et al., 1999), Mx-Cre x Cxcr4flox/flox mice (Sugiyama et al., 2006), and plt/plt mice (Nakano et al., 1998), as well as OT-I and OT-II TCR-transgenic and RIP-mOVA–transgenic mice (Kurts et al., >>1996<<; Barnden et al., 1998), were described previously.
n2:mentions: n3:9064352

Subject Item: _:vb10081306
rdf:type: n2:Context
rdf:value: mice (Förster et al., 1999), Mx-Cre x Cxcr4flox/flox mice (Sugiyama et al., 2006), and plt/plt mice (Nakano et al., 1998), as well as OT-I and OT-II TCR-transgenic and RIP-mOVA–transgenic mice (Kurts et al., 1996; Barnden et al., >>1998<<), were described previously.
n2:mentions: n3:9553774

Subject Item: _:vb10081307
rdf:type: n2:Context
rdf:value: mice were injected with poly I poly C, and only mice that exhibited a nearly complete loss of CXCR4 genomic sequence and the undetectable expression of CXCR4 gene in hematopoietic cells were further analyzed (Sugiyama et al., >>2006<<). Mice were maintained under specific pathogen-free conditions in our animal facility, and experiments were performed under the approval of the Institutional Animal Care Committee of the University of Tokushima.
n2:mentions: n3:17174120

Subject Item: _:vb10081308
rdf:type: n2:Context
rdf:value: Inflammatory lesions of the tissues were scored as previously described (Ishimaru et al., >>2008<<) and as follows:
n2:mentions: n3:19015307

Subject Item: _:vb10081309
rdf:type: n2:Context
rdf:value: were prepared by digesting thymic fragments with collagenase, dispase, and DNase I (Roche) and enriched by depleting CD45+ cells with a magnetic cell sorter (Miltenyi Biotec) before cell sorting, as described previously (Gray et al., >>2002<<). For DC analysis, thymus cells were prepared by digesting thymic fragments with collagenase D and DNase I.
n2:mentions: n3:11792372

Subject Item: _:vb10081310
rdf:type: n2:Context
rdf:value: According to the methods previously reported (Tai et al., >>2005<<), 5 × 104 CFSE-labeled CD4+CD25− lymph node T cells isolated from B6-Ly5.1 mice were cultured with 5 × 104 CD25+CD4+CD8− or CD25−CD4+CD8− thymocytes in the presence of 105 20 Gy-irradiated T cell–depleted spleen cells from B6 mice and 1
n2:mentions: n3:15640801

Subject Item: _:vb10081311
rdf:type: n4:Section
dc:title: results
n4:contains: _:vb10081328 _:vb10081329 _:vb10081330 _:vb10081331 _:vb10081332 _:vb10081333 _:vb10081334 _:vb10081320 _:vb10081321 _:vb10081322 _:vb10081323 _:vb10081324 _:vb10081325 _:vb10081326 _:vb10081327 _:vb10081312 _:vb10081313 _:vb10081314 _:vb10081315 _:vb10081316 _:vb10081317 _:vb10081318 _:vb10081319

Subject Item: _:vb10081312
rdf:type: n2:Context
rdf:value: tDCs are predominantly accumulated in the medulla and sparsely detectable in the cortex (Barclay and Mayrhofer, >>1981<<; Flotte et al., 1983; Kurobe et al., 2006). To identify chemokines that mediate the medullary accumulation of tDCs, we screened for the expression of chemokine receptors in isolated tDCs by RT-PCR analysis.
n2:mentions: n3:6942092

Subject Item: _:vb10081313
rdf:type: n2:Context
rdf:value: tDCs are predominantly accumulated in the medulla and sparsely detectable in the cortex (Barclay and Mayrhofer, 1981; Flotte et al., >>1983<<; Kurobe et al., 2006). To identify chemokines that mediate the medullary accumulation of tDCs, we screened for the expression of chemokine receptors in isolated tDCs by RT-PCR analysis.
n2:mentions: n3:6340516

Subject Item: _:vb10081314
rdf:type: n2:Context
rdf:value: tDCs are predominantly accumulated in the medulla and sparsely detectable in the cortex (Barclay and Mayrhofer, 1981; Flotte et al., 1983; Kurobe et al., >>2006<<). To identify chemokines that mediate the medullary accumulation of tDCs, we screened for the expression of chemokine receptors in isolated tDCs by RT-PCR analysis.
n2:mentions: n3:16473829

Subject Item: _:vb10081315
rdf:type: n2:Context
rdf:value: 1 C; Kurobe et al., >>2006<<; Nitta et al., 2009). Thus, instead of CCR7 and CXCR4, the XCL1–XCR1 chemokine axis may play a major role in regulating the medullary accumulation of tDCs.
n2:mentions: n3:16473829

Subject Item: _:vb10081316
rdf:type: n2:Context
rdf:value: 1 C; Kurobe et al., 2006; Nitta et al., >>2009<<). Thus, instead of CCR7 and CXCR4, the XCL1–XCR1 chemokine axis may play a major role in regulating the medullary accumulation of tDCs.
n2:mentions: n3:19805112

Subject Item: _:vb10081317
rdf:type: n2:Context
rdf:value: In addition to mTECs, Xcl1 was also detected in a small subpopulation of CD45+ thymocytes expressing NK1.1, including NK1.1+CD3− NK cells and NK1.1+CD3+ NKT cells (Kelner et al., >>1994<<; Hedrick et al., 1997; unpublished data).
n2:mentions: n3:7973732

Subject Item: _:vb10081318
rdf:type: n2:Context
rdf:value: In addition to mTECs, Xcl1 was also detected in a small subpopulation of CD45+ thymocytes expressing NK1.1, including NK1.1+CD3− NK cells and NK1.1+CD3+ NKT cells (Kelner et al., 1994; Hedrick et al., >>1997<<; unpublished data).
n2:mentions: n3:9029087

Subject Item: _:vb10081319
rdf:type: n2:Context
rdf:value: Previous studies showed that Xcl1 is expressed in the secondary lymphoid organs by Th1-polarized CD4+ T cells and activated CD8+ T cells (Dorner et al., >>2002<<, 2009). The expression of Xcl1 in mTECs was lower than that in activated CD8+ T cells (Fig. 2 F). However, in the thymus, XCL1 is prominently produced by a fraction of mTECs, whereas its receptor XCR1 is exclusively expressed by tDCs.
n2:mentions: n3:11972057

Subject Item: _:vb10081320
rdf:type: n2:Context
rdf:value: Previous studies showed that Xcl1 is expressed in the secondary lymphoid organs by Th1-polarized CD4+ T cells and activated CD8+ T cells (Dorner et al., 2002, >>2009<<). The expression of Xcl1 in mTECs was lower than that in activated CD8+ T cells (Fig. 2 F). However, in the thymus, XCL1 is prominently produced by a fraction of mTECs, whereas its receptor XCR1 is exclusively expressed by tDCs.
n2:mentions: n3:19913446

Subject Item: _:vb10081321
rdf:type: n2:Context
rdf:value: It was previously shown that tDCs contribute to the negative selection of self-reactive thymocytes (Jenkinson et al., >>1992<<; Gallegos and Bevan, 2004). We therefore examined whether negative selection might be affected in the thymus of Xcl1-deficient mice.
n2:mentions: n3:1512547

Subject Item: _:vb10081322
rdf:type: n2:Context
rdf:value: It was previously shown that tDCs contribute to the negative selection of self-reactive thymocytes (Jenkinson et al., 1992; Gallegos and Bevan, >>2004<<). We therefore examined whether negative selection might be affected in the thymus of Xcl1-deficient mice.
n2:mentions: n3:15492126

Subject Item: _:vb10081323
rdf:type: n2:Context
rdf:value: As tDCs have been implicated for their roles in negative selection by mammary tumor virus (Mtv)–encoded superantigens (Moore et al., >>1994<<), we first analyzed the negative selection of Vβ3+, Vβ5+, and Vβ11+ T cells in Mtv-expressing BALB/c mice.
n2:mentions: n3:8176205

Subject Item: _:vb10081324
rdf:type: n2:Context
rdf:value: We then examined whether negative selection of 2C-TCR–transgenic thymocytes reactive to systemically expressed self-antigens (Sha et al., >>1988<<) might be affected by Xcl1 deficiency. We found that the deletion of 2C-TCR+CD4+CD8+ thymocytes in negatively selecting H-2k/d mice appeared undisturbed in the absence of XCL1 (Fig.
n2:mentions: n3:3263574

Subject Item: _:vb10081325
rdf:type: n2:Context
rdf:value: tDCs are known to cooperate with mTECs in the negative selection of thymocytes reactive to tissue-restricted antigens (Gallegos and Bevan, >>2004<<). The rat insulin promoter (RIP)–driven transgene of membrane-bound OVA (mOVA) is expressed in the thymus by mTECs and deletes OVA-reactive OT-I-TCR and OT-II-TCR–transgenic thymocytes (Kurts et al., 1996). We found in irradiation-induced
n2:mentions: n3:15492126

Subject Item: _:vb10081326
rdf:type: n2:Context
rdf:value: The rat insulin promoter (RIP)–driven transgene of membrane-bound OVA (mOVA) is expressed in the thymus by mTECs and deletes OVA-reactive OT-I-TCR and OT-II-TCR–transgenic thymocytes (Kurts et al., >>1996<<). We found in irradiation-induced bone marrow chimera experiments that both OT-I-TCR–transgenic CD4−CD8+ and OT-II-TCR–transgenic CD4+CD8− thymocytes were deleted in the thymic microenvironments of RIP-mOVA–transgenic mice even in the
n2:mentions: n3:9064352

Subject Item: _:vb10081327
rdf:type: n2:Context
rdf:value: It was also shown that tDCs play a role in the thymic generation of nT reg cells (Watanabe et al., >>2005<<; Proietto et al., 2008; Hanabuchi et al., 2010). We thus examined whether the generation of nT reg cells in the thymus might be affected in Xcl1-deficient mice.
n2:mentions: n3:16121185

Subject Item: _:vb10081328
rdf:type: n2:Context
rdf:value: It was also shown that tDCs play a role in the thymic generation of nT reg cells (Watanabe et al., 2005; Proietto et al., >>2008<<; Hanabuchi et al., 2010). We thus examined whether the generation of nT reg cells in the thymus might be affected in Xcl1-deficient mice.
n2:mentions: n3:19073916

Subject Item: _:vb10081329
rdf:type: n2:Context
rdf:value: It was also shown that tDCs play a role in the thymic generation of nT reg cells (Watanabe et al., 2005; Proietto et al., 2008; Hanabuchi et al., >>2010<<). We thus examined whether the generation of nT reg cells in the thymus might be affected in Xcl1-deficient mice.
n2:mentions: n3:20173030

Subject Item: _:vb10081330
rdf:type: n2:Context
rdf:value: A majority of Foxp3+ nT reg cells in the thymus were localized in the medullary region (Fontenot et al., >>2005<<; also shown in Fig.
n2:mentions: n3:15780990

Subject Item: _:vb10081331
rdf:type: n2:Context
rdf:value: However, the number of thymic nT reg cell–derived spleen nT reg cells, which were identified by the expression of the nuclear factor Helios along with Foxp3 (Sugimoto et al., >>2006<<; Thornton et al., 2010), was reduced in Xcl1-deficient mice (Fig.
n2:mentions: n3:16772372

Subject Item: _:vb10081332
rdf:type: n2:Context
rdf:value: However, the number of thymic nT reg cell–derived spleen nT reg cells, which were identified by the expression of the nuclear factor Helios along with Foxp3 (Sugimoto et al., 2006; Thornton et al., >>2010<<), was reduced in Xcl1-deficient mice (Fig.
n2:mentions: n3:20181882

Subject Item: _:vb10081333
rdf:type: n2:Context
rdf:value: It was previously shown that Aire+ mTECs play a role in the thymic generation of T reg cells (Aschenbrenner et al., >>2007<<). Finally, we wished to examine whether the expression of Aire might be affected in the thymus of Xcl1-deficient mice and whether the expression of XCL1 might be affected in the thymus of Aire-deficient mice.
n2:mentions: n3:17322887

Subject Item: _:vb10081334
rdf:type: n2:Context
rdf:value: As has been recently reported (Laan et al., >>2009<<), the expression of other chemokines, such as Ccl19, Ccl21, and Ccl25, in mTECs was also modulated by the Aire deficiency (Fig.
n2:mentions: n3:19923453

Subject Item: _:vb10081335
rdf:type: n4:Section
dc:title: discussion
n4:contains: _:vb10081336 _:vb10081337 _:vb10081338 _:vb10081339 _:vb10081340 _:vb10081341 _:vb10081342 _:vb10081343 _:vb10081384 _:vb10081385 _:vb10081376 _:vb10081377 _:vb10081378 _:vb10081379 _:vb10081380 _:vb10081381 _:vb10081382 _:vb10081383 _:vb10081368 _:vb10081369 _:vb10081370 _:vb10081371 _:vb10081372 _:vb10081373 _:vb10081374 _:vb10081375 _:vb10081360 _:vb10081361 _:vb10081362 _:vb10081363 _:vb10081364 _:vb10081365 _:vb10081366 _:vb10081367 _:vb10081352 _:vb10081353 _:vb10081354 _:vb10081355 _:vb10081356 _:vb10081357 _:vb10081358 _:vb10081359 _:vb10081344 _:vb10081345 _:vb10081346 _:vb10081347 _:vb10081348 _:vb10081349 _:vb10081350 _:vb10081351

Subject Item: _:vb10081336
rdf:type: n2:Context
rdf:value: It is well known that tDCs are detected abundantly in the medullary region and sparsely in the cortical region (Barclay and Mayrhofer, >>1981<<; Flotte et al., 1983; Kurobe et al., 2006). However, the molecular mechanisms that contribute to this medullary accumulation of tDCs are unknown.
n2:mentions: n3:6942092

Subject Item: _:vb10081337
rdf:type: n2:Context
rdf:value: It is well known that tDCs are detected abundantly in the medullary region and sparsely in the cortical region (Barclay and Mayrhofer, 1981; Flotte et al., >>1983<<; Kurobe et al., 2006). However, the molecular mechanisms that contribute to this medullary accumulation of tDCs are unknown.
n2:mentions: n3:6340516

Subject Item: _:vb10081338
rdf:type: n2:Context
rdf:value: It is well known that tDCs are detected abundantly in the medullary region and sparsely in the cortical region (Barclay and Mayrhofer, 1981; Flotte et al., 1983; Kurobe et al., >>2006<<). However, the molecular mechanisms that contribute to this medullary accumulation of tDCs are unknown.
n2:mentions: n3:16473829

Subject Item: _:vb10081339
rdf:type: n2:Context
rdf:value: XCL1, which is also known as lymphotactin, ATAC, and SCM1, is the only member of the C family of chemokines encoded in the mouse genome (Kelner et al., >>1994<<). XCL1 is produced by activated CD8+ T cells, Th1-polarized CD4+ T cells, and NK cells (Kelner et al., 1994; Hedrick et al., 1997; Dorner et al., 2002, 2004, 2009).
n2:mentions: n3:7973732

Subject Item: _:vb10081340
rdf:type: n2:Context
rdf:value: XCL1 is produced by activated CD8+ T cells, Th1-polarized CD4+ T cells, and NK cells (Kelner et al., >>1994<<; Hedrick et al., 1997; Dorner et al., 2002, 2004, 2009).
n2:mentions: n3:7973732

Subject Item: _:vb10081341
rdf:type: n2:Context
rdf:value: XCL1 is produced by activated CD8+ T cells, Th1-polarized CD4+ T cells, and NK cells (Kelner et al., 1994; Hedrick et al., >>1997<<; Dorner et al., 2002, 2004, 2009).
n2:mentions: n3:9029087

Subject Item: _:vb10081342
rdf:type: n2:Context
rdf:value: XCL1 is produced by activated CD8+ T cells, Th1-polarized CD4+ T cells, and NK cells (Kelner et al., 1994; Hedrick et al., 1997; Dorner et al., >>2002<<, 2004, 2009).
n2:mentions: n3:11972057

Subject Item: _:vb10081343
rdf:type: n2:Context
rdf:value: XCL1 is produced by activated CD8+ T cells, Th1-polarized CD4+ T cells, and NK cells (Kelner et al., 1994; Hedrick et al., 1997; Dorner et al., 2002, >>2004<<, 2009). A recent study shows that the XCL1 receptor, XCR1, is expressed by CD8+ DCs in the spleen and that the XCL1-XCR1–mediated interaction between CD8+ T cells and CD8+ DCs is important for the development of cytotoxicity of CD8+ T
n2:mentions: n3:14978118

Subject Item: _:vb10081344
rdf:type: n2:Context
rdf:value: XCL1 is produced by activated CD8+ T cells, Th1-polarized CD4+ T cells, and NK cells (Kelner et al., 1994; Hedrick et al., 1997; Dorner et al., 2002, 2004, >>2009<<). A recent study shows that the XCL1 receptor, XCR1, is expressed by CD8+ DCs in the spleen and that the XCL1-XCR1–mediated interaction between CD8+ T cells and CD8+ DCs is important for the development of cytotoxicity of CD8+ T cells to
n2:mentions: n3:19913446

Subject Item: _:vb10081345
rdf:type: n2:Context
rdf:value: expressed by CD8+ DCs in the spleen and that the XCL1-XCR1–mediated interaction between CD8+ T cells and CD8+ DCs is important for the development of cytotoxicity of CD8+ T cells to antigens cross-presented by CD8+ DCs (Dorner et al., >>2009<<). However, the functions of the XCL1–XCR1 chemokine axis in the thymus have remained unknown.
n2:mentions: n3:19913446

Subject Item: _:vb10081346
rdf:type: n2:Context
rdf:value: Among the tDC subpopulations, XCR1 is most highly detectable in I-AhighCD11chighCD11b− lymphoid DCs, a population that largely overlaps with the CD8+Sirpα− conventional DC subpopulation of tDCs (Wu and Shortman, >>2005<<). In contrast, XCL1 in the thymus is expressed in the class II MHChigh subpopulation of mTECs in addition to NK and NKT cells. The Xcl1 transcripts expressed by mTECs are in smaller amounts than those expressed by activated CD8+ T cells
n2:mentions: n3:15946853

Subject Item: _:vb10081347
rdf:type: n2:Context
rdf:value: Aire is a nuclear factor expressed by a subpopulation of mTECs and is implicated for its role in the promiscuous gene expression of tissue-restricted self-antigens in mTECs (Derbinski et al., >>2005<<; Mathis and Benoist, 2009).
n2:mentions: n3:15983066

Subject Item: _:vb10081348
rdf:type: n2:Context
rdf:value: Aire is a nuclear factor expressed by a subpopulation of mTECs and is implicated for its role in the promiscuous gene expression of tissue-restricted self-antigens in mTECs (Derbinski et al., 2005; Mathis and Benoist, >>2009<<). It is also suggested that Aire regulates the development of mTECs, thereby indirectly contributing to the promiscuous gene expression in mTECs (Gillard et al., 2007; Yano et al., 2008). Our results show that the expression of Xcl1
n2:mentions: n3:19302042

Subject Item: _:vb10081349
rdf:type: n2:Context
rdf:value: It is also suggested that Aire regulates the development of mTECs, thereby indirectly contributing to the promiscuous gene expression in mTECs (Gillard et al., >>2007<<; Yano et al., 2008).
n2:mentions: n3:17312146

Subject Item: _:vb10081350
rdf:type: n2:Context
rdf:value: It is also suggested that Aire regulates the development of mTECs, thereby indirectly contributing to the promiscuous gene expression in mTECs (Gillard et al., 2007; Yano et al., >>2008<<). Our results show that the expression of Xcl1 transcripts in mTECs isolated from Aire-deficient mice is severely reduced to ∼1% of the amount observed in WT mTECs. Accordingly, as in Xcl1-deficient mice, the medullary accumulation of
n2:mentions: n3:19015306

Subject Item: _:vb10081351
rdf:type: n2:Context
rdf:value: Most T reg cells in the thymus are generated in the medullary region (Fontenot et al., >>2005<<) and it is suggested that mTECs (Aschenbrenner et al., 2007; Spence and Green, 2008), tDCs (Proietto et al., 2008; Hanabuchi et al., 2010), and their cooperation (Watanabe et al., 2005) contribute to the generation of T reg cells in the
n2:mentions: n3:15780990

Subject Item: _:vb10081352
rdf:type: n2:Context
rdf:value: Most T reg cells in the thymus are generated in the medullary region (Fontenot et al., 2005) and it is suggested that mTECs (Aschenbrenner et al., >>2007<<; Spence and Green, 2008), tDCs (Proietto et al., 2008; Hanabuchi et al., 2010), and their cooperation (Watanabe et al., 2005) contribute to the generation of T reg cells in the thymus.
n2:mentions: n3:17322887

Subject Item: _:vb10081353
rdf:type: n2:Context
rdf:value: Most T reg cells in the thymus are generated in the medullary region (Fontenot et al., 2005) and it is suggested that mTECs (Aschenbrenner et al., 2007; Spence and Green, >>2008<<), tDCs (Proietto et al., 2008; Hanabuchi et al., 2010), and their cooperation (Watanabe et al., 2005) contribute to the generation of T reg cells in the thymus.
n2:mentions: n3:18198277

Subject Item: _:vb10081354
rdf:type: n2:Context
rdf:value: Most T reg cells in the thymus are generated in the medullary region (Fontenot et al., 2005) and it is suggested that mTECs (Aschenbrenner et al., 2007; Spence and Green, 2008), tDCs (Proietto et al., >>2008<<; Hanabuchi et al., 2010), and their cooperation (Watanabe et al., 2005) contribute to the generation of T reg cells in the thymus.
n2:mentions: n3:19073916

Subject Item: _:vb10081355
rdf:type: n2:Context
rdf:value: Most T reg cells in the thymus are generated in the medullary region (Fontenot et al., 2005) and it is suggested that mTECs (Aschenbrenner et al., 2007; Spence and Green, 2008), tDCs (Proietto et al., 2008; Hanabuchi et al., >>2010<<), and their cooperation (Watanabe et al., 2005) contribute to the generation of T reg cells in the thymus.
n2:mentions: n3:20173030

Subject Item: _:vb10081356
rdf:type: n2:Context
rdf:value: in the medullary region (Fontenot et al., 2005) and it is suggested that mTECs (Aschenbrenner et al., 2007; Spence and Green, 2008), tDCs (Proietto et al., 2008; Hanabuchi et al., 2010), and their cooperation (Watanabe et al., >>2005<<) contribute to the generation of T reg cells in the thymus. Our results indicate that the deficiency of either Xcl1 or Aire causes the reduced generation of T reg cells in the thymus.
n2:mentions: n3:16121185

Subject Item: _:vb10081357
rdf:type: n2:Context
rdf:value: Proximal interactions between tDCs and mTECs in the thymic medulla may promote optimal generation of nT reg cells, possibly via the production of γc cytokines, including IL-2, IL-7, and thymic stromal lymphopoietin (Watanabe et al., >>2005<<; Ziegler and Liu, 2006; Mazzucchelli et al., 2008; Vang et al., 2008). Among the tDC subpopulations, lymphoid DCs most highly express XCR1 and, thus, may play a major role in the interaction with mTECs and the generation of nT reg cells.
n2:mentions: n3:16121185

Subject Item: _:vb10081358
rdf:type: n2:Context
rdf:value: between tDCs and mTECs in the thymic medulla may promote optimal generation of nT reg cells, possibly via the production of γc cytokines, including IL-2, IL-7, and thymic stromal lymphopoietin (Watanabe et al., 2005; Ziegler and Liu, >>2006<<; Mazzucchelli et al., 2008; Vang et al., 2008). Among the tDC subpopulations, lymphoid DCs most highly express XCR1 and, thus, may play a major role in the interaction with mTECs and the generation of nT reg cells.
n2:mentions: n3:16785889

Subject Item: _:vb10081359
rdf:type: n2:Context
rdf:value: the thymic medulla may promote optimal generation of nT reg cells, possibly via the production of γc cytokines, including IL-2, IL-7, and thymic stromal lymphopoietin (Watanabe et al., 2005; Ziegler and Liu, 2006; Mazzucchelli et al., >>2008<<; Vang et al., 2008). Among the tDC subpopulations, lymphoid DCs most highly express XCR1 and, thus, may play a major role in the interaction with mTECs and the generation of nT reg cells.
n2:mentions: n3:18664628

Subject Item: _:vb10081360
rdf:type: n2:Context
rdf:value: may promote optimal generation of nT reg cells, possibly via the production of γc cytokines, including IL-2, IL-7, and thymic stromal lymphopoietin (Watanabe et al., 2005; Ziegler and Liu, 2006; Mazzucchelli et al., 2008; Vang et al., >>2008<<). Among the tDC subpopulations, lymphoid DCs most highly express XCR1 and, thus, may play a major role in the interaction with mTECs and the generation of nT reg cells.
n2:mentions: n3:18714000

Subject Item: _:vb10081361
rdf:type: n2:Context
rdf:value: diphtheria toxin A under the control of a loxP-flanked neomycin resistance cassette from the ROSA26 locus has shown that these DC-depleted mice are not defective in the generation of nT reg cells in the thymus (Ohnmacht et al., >>2009<<), potentially contradicting our results indicating the role of tDCs in nT reg cell generation.
n2:mentions: n3:19237601

Subject Item: _:vb10081362
rdf:type: n2:Context
rdf:value: However, that work also described that the depletion of tDCs is incomplete in the DC-depleted mice (Ohnmacht et al., >>2009<<) but did not describe the intrathymic localization of the remaining tDCs.
n2:mentions: n3:19237601

Subject Item: _:vb10081363
rdf:type: n2:Context
rdf:value: However, several studies have described that the generation of T reg cells is not defective in Aire-deficient mice (Anderson et al., >>2002<<, 2005; Liston et al., 2003; Kuroda et al., 2005; Hubert et al., 2009), particularly in the spleen and the lymph nodes (Anderson et al., 2005; Kuroda et al., 2005; Hubert et al., 2009).
n2:mentions: n3:12376594

Subject Item: _:vb10081364
rdf:type: n2:Context
rdf:value: However, several studies have described that the generation of T reg cells is not defective in Aire-deficient mice (Anderson et al., 2002, >>2005<<; Liston et al., 2003; Kuroda et al., 2005; Hubert et al., 2009), particularly in the spleen and the lymph nodes (Anderson et al., 2005; Kuroda et al., 2005; Hubert et al., 2009).
n2:mentions: n3:16111640

Subject Item: _:vb10081365
rdf:type: n2:Context
rdf:value: However, several studies have described that the generation of T reg cells is not defective in Aire-deficient mice (Anderson et al., 2002, 2005; Liston et al., >>2003<<; Kuroda et al., 2005; Hubert et al., 2009), particularly in the spleen and the lymph nodes (Anderson et al., 2005; Kuroda et al., 2005; Hubert et al., 2009).
n2:mentions: n3:12612579

Subject Item: _:vb10081366
rdf:type: n2:Context
rdf:value: However, several studies have described that the generation of T reg cells is not defective in Aire-deficient mice (Anderson et al., 2002, 2005; Liston et al., 2003; Kuroda et al., >>2005<<; Hubert et al., 2009), particularly in the spleen and the lymph nodes (Anderson et al., 2005; Kuroda et al., 2005; Hubert et al., 2009).
n2:mentions: n3:15699112

Subject Item: _:vb10081367
rdf:type: n2:Context
rdf:value: However, several studies have described that the generation of T reg cells is not defective in Aire-deficient mice (Anderson et al., 2002, 2005; Liston et al., 2003; Kuroda et al., 2005; Hubert et al., >>2009<<), particularly in the spleen and the lymph nodes (Anderson et al., 2005; Kuroda et al., 2005; Hubert et al., 2009).
n2:mentions: n3:19265170

Subject Item: _:vb10081368
rdf:type: n2:Context
rdf:value: that the generation of T reg cells is not defective in Aire-deficient mice (Anderson et al., 2002, 2005; Liston et al., 2003; Kuroda et al., 2005; Hubert et al., 2009), particularly in the spleen and the lymph nodes (Anderson et al., >>2005<<; Kuroda et al., 2005; Hubert et al., 2009).
n2:mentions: n3:16111640

Subject Item: _:vb10081369
rdf:type: n2:Context
rdf:value: of T reg cells is not defective in Aire-deficient mice (Anderson et al., 2002, 2005; Liston et al., 2003; Kuroda et al., 2005; Hubert et al., 2009), particularly in the spleen and the lymph nodes (Anderson et al., 2005; Kuroda et al., >>2005<<; Hubert et al., 2009).
n2:mentions: n3:15699112

Subject Item: _:vb10081370
rdf:type: n2:Context
rdf:value: defective in Aire-deficient mice (Anderson et al., 2002, 2005; Liston et al., 2003; Kuroda et al., 2005; Hubert et al., 2009), particularly in the spleen and the lymph nodes (Anderson et al., 2005; Kuroda et al., 2005; Hubert et al., >>2009<<). Indeed, our results show that the number of T reg cells in Aire-deficient mice is reduced in the thymus to approximately half of that in WT mice but is not reduced in the spleen and the lymph nodes of Aire-deficient mice.
n2:mentions: n3:19265170

Subject Item: _:vb10081371
rdf:type: n2:Context
rdf:value: be noted that previous studies have indicated that the number of T reg cells in the thymus is slightly reduced in Aire-deficient mice, although those studies concluded no loss of T reg cell generation in the thymus (Anderson et al., >>2005<<; Kuroda et al., 2005; Hubert et al., 2009).
n2:mentions: n3:16111640

Subject Item: _:vb10081372
rdf:type: n2:Context
rdf:value: studies have indicated that the number of T reg cells in the thymus is slightly reduced in Aire-deficient mice, although those studies concluded no loss of T reg cell generation in the thymus (Anderson et al., 2005; Kuroda et al., >>2005<<; Hubert et al., 2009).
n2:mentions: n3:15699112

Subject Item: _:vb10081373
rdf:type: n2:Context
rdf:value: that the number of T reg cells in the thymus is slightly reduced in Aire-deficient mice, although those studies concluded no loss of T reg cell generation in the thymus (Anderson et al., 2005; Kuroda et al., 2005; Hubert et al., >>2009<<). We think that Aire indeed contributes to the optimal generation of nT reg cells in the thymus and that the generation of induced T reg cells, particularly in the periphery (Piccirillo and Shevach, 2004; Curotto de Lafaille and Lafaille,
n2:mentions: n3:19265170

Subject Item: _:vb10081374
rdf:type: n2:Context
rdf:value: We think that Aire indeed contributes to the optimal generation of nT reg cells in the thymus and that the generation of induced T reg cells, particularly in the periphery (Piccirillo and Shevach, >>2004<<; Curotto de Lafaille and Lafaille, 2009), has veiled the reduced cellularity of nT reg cells in Aire-deficient mice.
n2:mentions: n3:15036231

Subject Item: _:vb10081375
rdf:type: n2:Context
rdf:value: think that Aire indeed contributes to the optimal generation of nT reg cells in the thymus and that the generation of induced T reg cells, particularly in the periphery (Piccirillo and Shevach, 2004; Curotto de Lafaille and Lafaille, >>2009<<), has veiled the reduced cellularity of nT reg cells in Aire-deficient mice.
n2:mentions: n3:19464985

Subject Item: _:vb10081376
rdf:type: n2:Context
rdf:value: In a similar manner, Aire-deficient mice tend to exhibit inflammatory failure of exocrine tissues, including lacrimal glands (Anderson et al., >>2002<<, 2005; Kuroda et al., 2005; Hubert et al., 2009).
n2:mentions: n3:12376594

Subject Item: _:vb10081377
rdf:type: n2:Context
rdf:value: In a similar manner, Aire-deficient mice tend to exhibit inflammatory failure of exocrine tissues, including lacrimal glands (Anderson et al., 2002, >>2005<<; Kuroda et al., 2005; Hubert et al., 2009).
n2:mentions: n3:16111640

Subject Item: _:vb10081378
rdf:type: n2:Context
rdf:value: In a similar manner, Aire-deficient mice tend to exhibit inflammatory failure of exocrine tissues, including lacrimal glands (Anderson et al., 2002, 2005; Kuroda et al., >>2005<<; Hubert et al., 2009).
n2:mentions: n3:15699112

Subject Item: _:vb10081379
rdf:type: n2:Context
rdf:value: In a similar manner, Aire-deficient mice tend to exhibit inflammatory failure of exocrine tissues, including lacrimal glands (Anderson et al., 2002, 2005; Kuroda et al., 2005; Hubert et al., >>2009<<). The commonness of the target organs may reflect a similarity in the breakdown of self-tolerance in Xcl1-deficient mice and Aire-deficient mice. Nonetheless, our results do not rule out the possibility that the absence of XCL1 in
n2:mentions: n3:19265170

Subject Item: _:vb10081380
rdf:type: n2:Context
rdf:value: In contrast, tDCs are known for their roles in negative selection, particularly in the intrathymic presentation of peripheral antigens, by cooperating with promiscuous gene expression in mTECs (Gallegos and Bevan, >>2004<<; Koble and Kyewski, 2009; Nitta et al., 2009) and by transport from the circulation (Bonasio et al., 2006).
n2:mentions: n3:15492126

Subject Item: _:vb10081381
rdf:type: n2:Context
rdf:value: tDCs are known for their roles in negative selection, particularly in the intrathymic presentation of peripheral antigens, by cooperating with promiscuous gene expression in mTECs (Gallegos and Bevan, 2004; Koble and Kyewski, >>2009<<; Nitta et al., 2009) and by transport from the circulation (Bonasio et al., 2006).
n2:mentions: n3:19564355

Subject Item: _:vb10081382
rdf:type: n2:Context
rdf:value: for their roles in negative selection, particularly in the intrathymic presentation of peripheral antigens, by cooperating with promiscuous gene expression in mTECs (Gallegos and Bevan, 2004; Koble and Kyewski, 2009; Nitta et al., >>2009<<) and by transport from the circulation (Bonasio et al., 2006).
n2:mentions: n3:19805112

Subject Item: _:vb10081383
rdf:type: n2:Context
rdf:value: intrathymic presentation of peripheral antigens, by cooperating with promiscuous gene expression in mTECs (Gallegos and Bevan, 2004; Koble and Kyewski, 2009; Nitta et al., 2009) and by transport from the circulation (Bonasio et al., >>2006<<). The tDCs that are mislocalized in the CMJ regions in the absence of XCL1 may be sufficient for the cross-presentation of mTEC-expressed tissue-restricted antigens and the negative selection of developing thymocytes reactive to those
n2:mentions: n3:16951687

Subject Item: _:vb10081384
rdf:type: n2:Context
rdf:value: In addition, recent studies indicated that DCs in the thymic cortex are capable of inducing the deletion of negatively selected thymocytes (McCaughtry et al., >>2008<<) and that CCR2 is involved in the accumulation of CD8−Sirpα+ tDC subpopulation in the thymic cortex and the intrathymic negative selection against blood-borne antigens (Baba et al., 2009).
n2:mentions: n3:18936237

Subject Item: _:vb10081385
rdf:type: n2:Context
rdf:value: selected thymocytes (McCaughtry et al., 2008) and that CCR2 is involved in the accumulation of CD8−Sirpα+ tDC subpopulation in the thymic cortex and the intrathymic negative selection against blood-borne antigens (Baba et al., >>2009<<). Thus, the XCL1-mediated medullary accumulation is not needed for the deletion of the majority of negatively selected thymocytes.
n2:mentions: n3:19675159

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