E-cadherin marks a subset of inflammatory dendritic cells that promote T cell-mediated colitis.
Dendritic cells (DCs) play a pivotal role in controlling the balance between tolerance and immunity in the intestine. Gut conditioned CD103(+) DCs promote regulatory T (Treg) cell responses; however, little is known about DCs that drive inflammation in the intestine. Here, we show that monocyte-derived inflammatory DCs that express E-cadherin, the receptor for CD103, promote intestinal inflammation. E-cadherin(+) DCs accumulated in the inflamed mesenteric lymph nodes and colon, had high expression of toll-like receptors, and produced colitogenic cytokines, such as IL-6 and IL-23, after activation. Importantly, adoptive transfer of E-cadherin(+) DCs into T cell-restored immunodeficient hosts increased Th17 cell responses in the intestine and led to exacerbation of colitis. These results identify a monocyte-derived inflammatory DC subset that is associated with the pathogenesis of intestinal inflammation, providing a therapeutic target for the treatment of inflammatory bowel disease.
Siddiqui
Karima R R
KR
Sir William Dunn School of Pathology, University of Oxford, OX1 3RE Oxford, UK.
Laffont
Sophie
S
Powrie
Fiona
F
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D015820:Cadherins / Q000276:immunology*; D002454:Cell Differentiation; D002465:Cell Movement; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D039001:Integrin alpha Chains / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D039521:CD11c Antigen; D015820:Cadherins; D039001:Integrin alpha Chains; C091367:alpha E integrins
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