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Science 329 (5993): 849-853

Copyright © 2010 by the American Association for the Advancement of Science

Activation of β-Catenin in Dendritic Cells Regulates Immunity Versus Tolerance in the Intestine

Santhakumar Manicassamy,1 Boris Reizis,2 Rajesh Ravindran,1 Helder Nakaya,1 Rosa Maria Salazar-Gonzalez,1,3 Yi-chong Wang,1 Bali Pulendran1,4,*

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–β-catenin signaling in intestinal dendritic cells regulates the balance between inflammatory versus regulatory responses in the gut. β-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–β, and the stimulation of regulatory T cell induction while suppressing inflammatory effector T cells. Furthermore, ablation of β-catenin expression in DCs enhanced inflammatory responses and disease in a mouse model of inflammatory bowel disease. Thus, β-catenin signaling programs DCs to a tolerogenic state, limiting the inflammatory response.

1 Emory Vaccine Center, and Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA.
2 Department of Microbiology, Columbia University Medical Center, New York, NY 10032, USA.
3 Molecular Immunology Division, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229–3039, USA.
4 Department of Pathology, Emory University, 1364 Clifton Road NE, Atlanta, GA 30322, USA.

* To whom correspondence should be addressed. E-mail: bpulend{at}emory.edu

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