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Epithelial microRNAs regulate gut mucosal immunity via epithelium-T cell crosstalk

Official URL:https://doi.org/10.1038/ni.1994
PubMed:View item in PubMed
Creators Name:Biton, M. and Levin, A. and Slyper, M. and Alkalay, I. and Horwitz, E. and Mor, H. and Kredo-Russo, S. and Avnit-Sagi, T. and Cojocaru, G. and Zreik, F. and Bentwich, Z. and Poy, M.N. and Artis, D. and Walker, M.D. and Hornstein, E. and Pikarsky, E. and Ben-Neriah, Y.
Journal Title:Nature Immunology
Journal Abbreviation:Nat Immunol
Page Range:239-246
Date:March 2011
Keywords:Cell Communication, Epithelium, Gastrointestinal Tract, HT29 Cells, Immunohistochemistry, Interleukin-13, MicroRNAs, Mucosal Immunity, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, T-Lymphocytes, Animals, Mice
Abstract:Colonic homeostasis entails epithelium-lymphocyte cooperation, yet many participants in this process are unknown. We show here that epithelial microRNAs mediate the mucosa-immune system crosstalk necessary for mounting protective T helper type 2 (T(H)2) responses. Abolishing the induction of microRNA by gut-specific deletion of Dicer1 (Dicer1(Deltagut)), which encodes an enzyme involved in microRNA biogenesis, deprived goblet cells of RELMbeta, a key T(H)2 antiparasitic cytokine; this predisposed the host to parasite infection. Infection of Dicer1(Deltagut) mice with helminths favored a futile T(H)1 response with hallmarks of inflammatory bowel disease. Interleukin 13 (IL-13) induced the microRNA miR-375, which regulates the expression of TSLP, a T(H)2-facilitating epithelial cytokine; this indicated a T(H)2-amplification loop. We found that miR-375 was required for RELMbeta expression in vivo; miR-375-deficient mice had significantly less intestinal RELMbeta, which possibly explains the greater susceptibility of Dicer1(Deltagut) mice to parasites. Our findings indicate that epithelial microRNAs are key regulators of gut homeostasis and mucosal immunity.
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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