E-Cadherin Marks a Subset of Inflammatory Dendritic Cells that Promote T Cell-Mediated Colitis

Summary

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.

Highlights

► E-cadherin ⁺ DCs accumulate in the inflamed MLN and colon ► E-cadherin ⁺ DCs derive mainly from Gr1 ⁺ inflammatory monocytes ► E-cadherin ⁺ DCs produce high amounts of inflammatory cytokines and chemokines ► E-cadherin ⁺ DCs exacerbate colitis