E-cadherin marks a subset of inflammatory dendritic cells that promote T cell-mediated colitis

Immunity. 2010 Apr 23;32(4):557-67. doi: 10.1016/j.immuni.2010.03.017. Epub 2010 Apr 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • CD11c Antigen / immunology
  • Cadherins / immunology*
  • Cell Differentiation
  • Cell Movement
  • Colitis / genetics
  • Colitis / immunology*
  • Colitis / pathology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Gene Expression Regulation
  • Immunity, Innate
  • Inflammation / immunology
  • Integrin alpha Chains / immunology
  • Mice
  • Mice, Inbred BALB C
  • Monocytes / cytology
  • Monocytes / immunology
  • T-Lymphocytes / immunology*

Substances

  • Antigens, CD
  • CD11c Antigen
  • Cadherins
  • Integrin alpha Chains
  • alpha E integrins