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Science. 2010 Aug 13;329(5993):849-53. doi: 10.1126/science.1188510.

Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine.

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1
Emory Vaccine Center, and Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA.

Erratum in

  • Science. 2011 Nov 4;334(6056):594.

Abstract

Dendritic cells (DCs) play a vital role in initiating robust immunity against pathogens as well as maintaining immunological tolerance to self antigens. However, the intracellular signaling networks that program DCs to become tolerogenic remain unknown. We report here that the Wnt-beta-catenin signaling in intestinal dendritic cells regulates the balance between inflammatory versus regulatory responses in the gut. beta-catenin in intestinal dendritic cells was required for the expression of anti-inflammatory mediators such as retinoic acid-metabolizing enzymes, interleukin-10, and transforming growth factor-beta, and the stimulation of regulatory T cell induction while suppressing inflammatory effector T cells. Furthermore, ablation of beta-catenin expression in DCs enhanced inflammatory responses and disease in a mouse model of inflammatory bowel disease. Thus, beta-catenin signaling programs DCs to a tolerogenic state, limiting the inflammatory response.

PMID:
20705860
PMCID:
PMC3732486
DOI:
10.1126/science.1188510
[Indexed for MEDLINE]
Free PMC Article

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