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

Item Type:	Article
Title:	CCR7 is critically important for migration of dendritic cells in intestinal lamina propria to mesenteric lymph nodes
Creators Name:	Jang, M.H. and Sougawa, N. and Tanaka, T. and Hirata, T. and Hiroi, T. and Tohya, K. and Guo, Z. and Umemoto, E. and Ebisuno, Y. and Yang, B.G. and Seoh, J.Y. and Lipp, M. and Kiyono, H. and Miyasaka, M.
Abstract:	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 MLNs. 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 MLNs, DCs bearing the unique LP-DC phenotype (CD11chighCD8αintCD11b lowαL lowβ7 high and CD11chighCD8α-CD11b highαL lowβ7 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 MLNs in a CCR7-dependent manner to engage in the presentation of IEC-associated Ags acquired in the LP.
Keywords:	Antigen Presentation, Apoptosis, Base Sequence, CC Chemokines, CCR7 Receptors, CD4-Positive T-Lymphocytes, Cell Differentiation, Cell Movement, Chemokine CCL21, Chemokine Receptors, DNA, Dendritic Cells, Endocytosis, Epithelial Cells, Gene Expression, Inbred BALB C Mice, Inbred C57BL Mice, Interleukin-10, Interleukin-4, Intestinal Mucosa, Knockout Mice, Lymph Nodes, Mutant Strains Mice, Transgenic Mice, Animals, Mice
Source:	Journal of Immunology
ISSN:	0022-1767
Publisher:	American Association of Immunologists
Volume:	176
Number:	2
Page Range:	803-810
Date:	15 January 2006
Official Publication:	http://www.jimmunol.org/cgi/content/abstract/176/2/803
PubMed:	View item in PubMed

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