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

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_H2) responses. Abolishing the induction of microRNA by gut-specific deletion of Dicer1 (Dicer1^Δgut), which encodes an enzyme involved in microRNA biogenesis, deprived goblet cells of RELMβ, a key T_H2 antiparasitic cytokine; this predisposed the host to parasite infection. Infection of Dicer1^Δgut mice with helminths favored a futile T_H1 response with hallmarks of inflammatory bowel disease. Interleukin 13 (IL-13) induced the microRNA miR-375, which regulates the expression of TSLP, a T_H2-facilitating epithelial cytokine; this indicated a T_H2-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 Dicer1^Δgut mice to parasites. Our findings indicate that epithelial microRNAs are key regulators of gut homeostasis and mucosal immunity. [ABSTRACT FROM AUTHOR]