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Intestinal dendritic cells specialize to activate transforming growth factor-? and induce Foxp3+ regulatory T cells via integrin ?v?8.

ABSTRACT:

Background & aims

The intestinal immune system is tightly regulated to prevent responses against the many nonpathogenic antigens in the gut. Transforming growth factor (TGF)-? is a cytokine that maintains intestinal homeostasis, in part by inducing Foxp3(+) regulatory T cells (Tregs) that suppress immune responses. TGF-? is expressed at high levels in the gastrointestinal tract as a latent complex that must be activated. However, the pathways that control TGF-? activation in the intestine are poorly defined. We investigated the cellular and molecular pathways that control activation of TGF-? and induction of Foxp3(+) Tregs in the intestines of mice to maintain immune homeostasis.

Methods

Subsets of intestinal dendritic cells (DCs) were examined for their capacity to activate TGF-? and induce Foxp3(+) Tregs in vitro. Mice were fed oral antigen, and induction of Foxp3(+) Tregs was measured.

Results

A tolerogenic subset of intestinal DCs that express CD103 were specialized to activate latent TGF-?, and induced Foxp3(+) Tregs independently of the vitamin A metabolite retinoic acid. The integrin ?v?8, which activates TGF-?, was significantly up-regulated on CD103(+) intestinal DCs. DCs that lack expression of integrin ?v?8 had reduced ability to activate latent TGF-? and induce Foxp3(+) Tregs in vitro and in vivo.

Conclusions

CD103(+) intestinal DCs promote a tolerogenic environment in the intestines of mice via integrin ?v?8-mediated activation of TGF-?.

SUBMITTER: Worthington JJ

PROVIDER: S-EPMC3507624 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Publications

Intestinal dendritic cells specialize to activate transforming growth factor-β and induce Foxp3+ regulatory T cells via integrin αvβ8.

Worthington John J JJ Czajkowska Beata I BI Melton Andrew C AC Travis Mark A MA

Gastroenterology 20110630 5

<h4>Background & aims</h4>The intestinal immune system is tightly regulated to prevent responses against the many nonpathogenic antigens in the gut. Transforming growth factor (TGF)-β is a cytokine that maintains intestinal homeostasis, in part by inducing Foxp3(+) regulatory T cells (Tregs) that suppress immune responses. TGF-β is expressed at high levels in the gastrointestinal tract as a latent complex that must be activated. However, the pathways that control TGF-β activation in the intestin ...[more]

PMID: 21723222

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