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

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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., Sougawa, N., Tanaka, T., Hirata, T., Hiroi, T., Tohya, K., Guo, Z., Umemoto, E., Ebisuno, Y., Yang, B.G., Seoh, J.Y., Lipp, M., 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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