The role of dendritic cells in the development of acute dextran sulfate sodium colitis

Peyer’s patches (PPs) simultaneously initiate active and quiescent immune responses in the gut. The immunological function is achieved by the rigid regulation of cell distribution and trafficking, but how the cell distribution is maintained remains to be elucidated. In this study, we show that binding of stromal cell–derived lymphoid chemokines to conventional dendritic cells (cDCs) is essential for the retention of naive CD4+ T cells in the interfollicular region (IFR) of PPs. Transitory depletion of CD11chigh cDCs in mice rapidly impaired the IFR structure in the PPs without affecting B cell follicles or germinal centers, lymphoid chemokine production from stromal cells, or the immigration of naive T cells into the IFRs of PPs. The cDC-orchestrated retention of naive T cells was mediated by heparinase-sensitive molecules that were expressed on cDCs and bound the lymphoid chemokine CCL21 produced from stromal cells. These data collectively reveal that interactions among cDCs, stromal cells, and naive T cells are necessary for the formation of IFRs in the PPs.

Section: Depletion Of Cdcs Decreases Naive Cd4 + T Cells In the Ppssupporting

confidence: 84%

Critical Role of Dendritic Cells in T Cell Retention in the Interfollicular Region of Peyer’s Patches

Obata

Shibata

Goto

et al. 2013

“…To definitively demonstrate a central role for cDC in our model of arthritis, we used CD11cDTR transgenic mice, which have been used to reveal the importance of these cells in a variety of experimental systems (22,(30)(31)(32)(33). It is reported that depletion is not entirely specific to cDCs, impacting on low expressers of CD11c (34).…”

Section: Transient Depletion Of Cd11c + Cells Reduced Articular Pathomentioning

confidence: 99%

Identifying the Cells Breaching Self-Tolerance in Autoimmunity

Benson¹,

Patakas

Conigliaro

et al. 2010

“…Dendritic cells (DCs) play a critical role in orchestrating the primary immune response and perform a key role in the generation of intestinal inflammation (32,33). Studies have revealed the expression of several 5-HT receptors on DCs, and functional studies have shown that 5-HT alters the cytokine profile of human DCs, enhancing the release of cytokines IL-1b and IL-8 (34).…”

mentioning

confidence: 99%

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Kim

Bridle

Ghia

et al. 2013

114

Mucosal inflammation in conditions ranging from infective acute enteritis or colitis to inflammatory bowel disease is accompanied by alteration in serotonin (5-hydroxytryptamine [5-HT]) content in the gut. Recently, we have identified an important role of 5-HT in the pathogenesis of experimental colitis. 5-HT type 7 (5-HT7) receptor is one of the most recently identified members of the 5-HT receptor family, and dendritic cells express this receptor. In this study, we investigated the effect of blocking 5-HT7 receptor signaling in experimental colitis with a view to develop an improved therapeutic strategy in intestinal inflammatory disorders. Colitis was induced with dextran sulfate sodium (DSS) or dinitrobenzene sulfonic acid (DNBS) in mice treated with selective 5-HT7 receptor antagonist SB-269970, as well as in mice lacking 5-HT7 receptor (5-HT7−/−) and irradiated wild-type mice reconstituted with bone marrow cells harvested from 5-HT7−/− mice. Inhibition of 5-HT7 receptor signaling with SB-269970 ameliorated both acute and chronic colitis induced by DSS. Treatment with SB-269970 resulted in lower clinical disease, histological damage, and proinflammatory cytokine levels compared with vehicle-treated mice post-DSS. Colitis severity was significantly lower in 5-HT7−/− mice and in mice reconstituted with bone marrow cells from 5-HT7−/− mice compared with control mice after DSS colitis. 5-HT7−/− mice also had significantly reduced DNBS-induced colitis. These observations provide us with novel information on the critical role of the 5-HT7 receptor in immune response and inflammation in the gut, and highlight the potential benefit of targeting this receptor to alleviate the severity of intestinal inflammatory disorders such as inflammatory bowel disease.