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

Gastroenterology. 2011 Nov;141(5):1802-12. doi: 10.1053/j.gastro.2011.06.057. Epub 2011 Jun 30.


Background & aims: 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 intestine are poorly defined. We investigated the cellular and molecular pathways that control activation of TGF-β 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-β 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-β, and induced Foxp3(+) Tregs independently of the vitamin A metabolite retinoic acid. The integrin αvβ8, which activates TGF-β, was significantly up-regulated on CD103(+) intestinal DCs. DCs that lack expression of integrin αvβ8 had reduced ability to activate latent TGF-β and induce Foxp3(+) Tregs in vitro and in vivo.

Conclusions: CD103(+) intestinal DCs promote a tolerogenic environment in the intestines of mice via integrin αvβ8-mediated activation of TGF-β.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / physiology*
  • Forkhead Transcription Factors / metabolism*
  • Homeostasis / physiology
  • Immune System / physiology
  • In Vitro Techniques
  • Integrin alpha Chains / metabolism
  • Integrins / genetics
  • Integrins / metabolism*
  • Intestines / cytology*
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Ovalbumin / pharmacology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / metabolism*
  • Transforming Growth Factor beta / metabolism*
  • Tretinoin / metabolism


  • Antigens, CD
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Integrin alpha Chains
  • Integrins
  • Transforming Growth Factor beta
  • alpha E integrins
  • integrin alphavbeta8
  • Tretinoin
  • Ovalbumin