| Literature DB >> 24792912 |
Dror S Shouval1, Amlan Biswas1, Jeremy A Goettel1, Katelyn McCann2, Evan Conaway3, Naresh S Redhu1, Ivan D Mascanfroni4, Ziad Al Adham5, Sydney Lavoie6, Mouna Ibourk6, Deanna D Nguyen7, Janneke N Samsom8, Johanna C Escher9, Raz Somech10, Batia Weiss11, Rita Beier12, Laurie S Conklin13, Christen L Ebens14, Fernanda G M S Santos15, Alexandre R Ferreira15, Mary Sherlock16, Atul K Bhan17, Werner Müller18, J Rodrigo Mora7, Francisco J Quintana4, Christoph Klein19, Aleixo M Muise20, Bruce H Horwitz21, Scott B Snapper22.
Abstract
Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on T cells, was critical for regulating mucosal homeostasis. Following wild-type (WT) CD4(+) T cell transfer, Rag2(-/-)Il10rb(-/-) mice developed severe colitis in association with profound defects in generation and function of Treg cells. Moreover, loss of IL-10R signaling impaired the generation and function of anti-inflammatory intestinal and bone-marrow-derived macrophages and their ability to secrete IL-10. Importantly, transfer of WT but not Il10rb(-/-) anti-inflammatory macrophages ameliorated colitis induction by WT CD4(+) T cells in Rag2(-/-)Il10rb(-/-) mice. Similar alterations in the generation and function of anti-inflammatory macrophages were observed in IL-10R-deficient patients with very early onset inflammatory bowel disease. Collectively, our studies define innate immune IL-10R signaling as a key factor regulating mucosal immune homeostasis in mice and humans.Entities:
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Year: 2014 PMID： 24792912 PMCID： PMC4513358 DOI： 10.1016/j.immuni.2014.03.011
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745