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

Moshe Biton, Avi Levin, Michal Slyper, Irit Alkalay, Elad Horwitz, Hagar Mor, Sharon Kredo-Russo, Tali Avnit-Sagi, Gady Cojocaru, Farid Zreik, Zvi Bentwich, Matthew N. Poy, David Artis, Michael D. Walker, Eran Hornstein, Eli Pikarsky, Yinon Ben-Neriah

Research output: Contribution to journalArticle

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 (TH2) responses. Abolishing the induction of microRNA by gut-specific deletion of Dicer1 (Dicer1δgut), which encodes an enzyme involved in microRNA biogenesis, deprived goblet cells of RELMβ, a key TH2 antiparasitic cytokine; this predisposed the host to parasite infection. Infection of Dicer1δgut mice with helminths favored a futile TH1 response with hallmarks of inflammatory bowel disease. Interleukin 13 (IL-13) induced the microRNA miR-375, which regulates the expression of TSLP, a TH2-facilitating epithelial cytokine; this indicated a TH2-amplification loop. We found that miR-375 was required for RELMβ expression in vivo; miR-375-deficient mice had significantly less intestinal RELMβ, which possibly explains the greater susceptibility of Dicer1δgut mice to parasites. Our findings indicate that epithelial microRNAs are key regulators of gut homeostasis and mucosal immunity.

Original languageEnglish (US)
Pages (from-to)239-246
Number of pages8
JournalNature Immunology
Volume12
Issue number3
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Biton, M., Levin, A., Slyper, M., Alkalay, I., Horwitz, E., Mor, H., Kredo-Russo, S., Avnit-Sagi, T., Cojocaru, G., Zreik, F., Bentwich, Z., Poy, M. N., Artis, D., Walker, M. D., Hornstein, E., Pikarsky, E., & Ben-Neriah, Y. (2011). Epithelial microRNAs regulate gut mucosal immunity via epithelium-T cell crosstalk. Nature Immunology, 12(3), 239-246. https://doi.org/10.1038/ni.1994