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CCR7 is critically important in intestinal lamina propria for migration of dendritic cells to mesenteric lymph nodes
- CCR7 is critically important in intestinal lamina propria for migration of dendritic cells to mesenteric lymph nodes
- 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
- Ewha Authors
- SCOPUS Author ID
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- Journal Title
- JOURNAL OF IMMUNOLOGY
- vol. 176, no. 2, pp. 803 - 810
- AMER ASSOC IMMUNOLOGISTS
- SCI; SCIE; SCOPUS
- 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(L)(low)beta(7) and CD11c(high)CD8 alpha(-)CD11b(high) alpha(L)(low)beta(7)(high)) 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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