CCR7 is critically important in intestinal lamina propria for migration of dendritic cells to mesenteric lymph nodes

被引:325
作者
Jang, MH
Sougawa, N
Tanaka, T
Hirata, T
Hiroi, T
Tohya, K
Guo, ZJ
Umemoto, E
Ebisuno, Y
Yang, BG
Seoh, JY
Lipp, M
Kiyono, H
Miyasaka, M
机构
[1] Osaka Univ, Grad Sch Med, Dept Microbiol & Immunol, Lab Immunodynam, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Res Inst Microbial Dis, Cent Ctr Excellence Program 21, Suita, Osaka, Japan
[3] Univ Tokyo, Inst Med Sci, Div Mucosal Immunol, Tokyo, Japan
[4] Kansai Coll Oriental Med, Dept Anat, Osaka, Japan
[5] Ewha Womans Univ, Coll Med, Dept Microbiol, Seoul, South Korea
[6] Max Delbruck Ctr Mol Med, Berlin, Germany
关键词
D O I
10.4049/jimmunol.176.2.803
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Although dendritic cells (DCs) located in the small intestinal lamina propria (LP-DCs) migrate to mesenteric lymph nodes (MLNs) constitutively, it is unclear which chemokines regulate their trafficking to NILNs. In this study we report that LP-DCs in unperturbed mice require CCR7 to migrate to MLNs. In vitro, LP-DCs expressing CCR7 migrated toward CCL21, although the LP-DCs appeared morphologically and phenotypically immature. In NILNs, DCs bearing the unique LP-DC phenotype (CD11c(high)CD8 alpha(int)CD11b(low)alpha(low)(L)beta(7) and CD11c(high)CD8 alpha(-)CD11b(high) alpha(low)(L)beta(high)(7)) were abundant in wild-type mice, but were markedly fewer in CCL19-, CCL21-Ser-deficient plt/plt mice and were almost absent in CCR7-deficient mice, indicating the critical importance of CCR7 in LP-DC trafficking to MLNs. Interestingly, CCR7(+) DCs in MLNs with the unique LP-DC phenotype had numerous vacuoles containing cellular debris in the cytoplasm, although MLN-DCs themselves were poorly phagocytic, suggesting that the debris was derived from the LP, where the LP-DCs ingested apoptotic intestinal epithelial cells (IECs). Consistent with this, LP-DCs ingested IECs vigorously in vitro. By presenting IEC-associated Ag, the LP-DCs also induce T cells to produce IL-4 and IL-10. Collectively, these results strongly suggest that LP-DCs with unique immunomodulatory activities migrate to NILNs in a CCR7-dependent manner to engage in the presentation of IEC-associated Ags acquired in the LP.
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页码:803 / 810
页数:8
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