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-derive...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2010-04, Vol.32 (4), p.557-567
Main Authors: Siddiqui, Karima R.R., Laffont, Sophie, Powrie, Fiona
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - immunology
Cadherins - immunology
CD11c Antigen - immunology
Cell Differentiation
Cell Movement
CELLIMMUNO
Colitis - genetics
Colitis - immunology
Colitis - pathology
Dendritic Cells - cytology
Dendritic Cells - immunology
Gene expression
Gene Expression Regulation
Homeostasis
Immunity, Innate
Inflammation - immunology
Inflammatory bowel disease
Integrin alpha Chains - immunology
Lymphocytes
Mice
Mice, Inbred BALB C
MOLIMMUNO
Monocytes - cytology
Monocytes - immunology
Population
Rodents
T-Lymphocytes - immunology
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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. ► 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
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2010.03.017