Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine.
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.
Manicassamy
Santhakumar
S
Emory Vaccine Center, and Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA.
Reizis
Boris
B
Ravindran
Rajesh
R
Nakaya
Helder
H
Salazar-Gonzalez
Rosa Maria
RM
Wang
Yi-Chong
YC
Pulendran
Bali
B
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D017634:Self Tolerance; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014212:Tretinoin / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
C495267:CTNNB1 protein, mouse; D016207:Cytokines; D051153:Wnt Proteins; D051176:beta Catenin; D014212:Tretinoin