title: CCR7 is critically important for migration of dendritic cells in intestinal lamina propria to mesenteric lymph nodes.
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 (CD11chighCD8alphaintCD11blowalphaLlowbeta7high and CD11chighCD8alpha-CD11bhighalphaLlowbeta7high) 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.
authors.affiliation: Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Myoung Ho
authors.initials: MH
authors.lastname: Jang
authors.forename: Nagako
authors.initials: N
authors.lastname: Sougawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Takako
authors.initials: T
authors.lastname: Hirata
authors.forename: Takachika
authors.initials: T
authors.lastname: Hiroi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tohya
authors.forename: Zijin
authors.initials: Z
authors.lastname: Guo
authors.forename: Eiji
authors.initials: E
authors.lastname: Umemoto
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Ebisuno
authors.forename: Bo-Gie
authors.initials: BG
authors.lastname: Yang
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Seoh
authors.forename: Martin
authors.initials: M
authors.lastname: Lipp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyasaka
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D002465:Cell Movement / Q000276:immunology / Q000502:physiology; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000378:metabolism; D004247:DNA / Q000235:genetics; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000502:physiology*; D004705:Endocytosis; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D015870:Gene Expression; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D016753:Interleukin-10; D015847:Interleukin-4; D004247:DNA