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

Santhakumar Manicassamy, Boris Reizis, Rajesh Ravindran, Helder Nakaya, Rosa Maria Salazar-Gonzalez, Yi Chong Wang, Bali Pulendran

Research output: Contribution to journalArticle

352 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)849-853
Number of pages5
JournalScience
Volume329
Issue number5993
DOIs
StatePublished - Aug 13 2010
Externally publishedYes

ASJC Scopus subject areas

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    Manicassamy, S., Reizis, B., Ravindran, R., Nakaya, H., Salazar-Gonzalez, R. M., Wang, Y. C., & Pulendran, B. (2010). Activation of β-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science, 329(5993), 849-853. https://doi.org/10.1126/science.1188510