Microbiota Sensing by Mincle-Syk Axis in Dendritic Cells Regulates Interleukin-17 and -22 Production and Promotes Intestinal Barrier Integrity

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2019 Feb 3

PMID 30709742

Citations 102

Authors

Maria Martinez-Lopez

Salvador Iborra

Ruth Conde-Garrosa

Annalaura Mastrangelo

Camille Danne

Elizabeth R Mann

Delyth M Reid

Valerie Gaboriau-Routhiau

Maria Chaparro

Maria P Lorenzo

Lara Minnerup

Paula Saz-Leal

Emma Slack

Benjamin Kemp

Javier P Gisbert

Andrzej Dzionek

Matthew J Robinson

Francisco J Ruperez

Nadine Cerf-Bensussan

Gordon D Brown

David Bernardo

Salome LeibundGut-Landmann

David Sancho

Affiliations

Soon will be listed here.

Abstract

Production of interleukin-17 (IL-17) and IL-22 by T helper 17 (Th17) cells and group 3 innate lymphoid cells (ILC3s) in response to the gut microbiota ensures maintenance of intestinal barrier function. Here, we examined the mechanisms whereby the immune system detects microbiota in the steady state. A Syk-kinase-coupled signaling pathway in dendritic cells (DCs) was critical for commensal-dependent production of IL-17 and IL-22 by CD4 T cells. The Syk-coupled C-type lectin receptor Mincle detected mucosal-resident commensals in the Peyer's patches (PPs), triggered IL-6 and IL-23p19 expression, and thereby regulated function of intestinal Th17- and IL-17-secreting ILCs. Mice deficient in Mincle or with selective depletion of Syk in CD11c cells had impaired production of intestinal RegIIIγ and IgA and increased systemic translocation of gut microbiota. Consequently, Mincle deficiency led to liver inflammation and deregulated lipid metabolism. Thus, sensing of commensals by Mincle and Syk signaling in CD11c cells reinforces intestinal immune barrier and promotes host-microbiota mutualism, preventing systemic inflammation.

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