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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Microbiota Sensing by Mincle-Syk Axis in Dendritic Cells Regulates Interleukin-17 and -22 Production and Promotes Intestinal Barrier Integrity
Immunity, Volume 50, No. 2, Year 2019
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Description
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. Martínez-López et al. explore host signaling pathways linking recognition of commensal microbes and Th17 differentiation. They find that the Mincle-Syk axis in Peyer's patch DCs detects mucosal-resident bacteria, inducing IL-6 and IL-23p19 and stimulating IL-17 and IL-22 production by intestinal T cells and ILCs, which control the intestinal immune barrier function. © 2018 The Author(s)
Authors & Co-Authors
Reid, Delyth M.
United Kingdom, London
Medical Research Council
Slack, Emma Caroline
Switzerland, Zurich
Eth Zürich
Gisbert, Javier Pérez
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
Robinson, Matthew J.
United Kingdom, Cambridge
Medimmune Limited, Cambridge
Cerf-Bensussan, Nadine
France, Paris
Inserm
France, Paris
Université Paris Cité
Brown, Gordon D.A.
United Kingdom, London
Medical Research Council
LeibundGut-Landmann, Salomé
Switzerland, Zurich
Vetsuisse-fakultät
Statistics
Citations: 128
Authors: 7
Affiliations: 15
Identifiers
Doi:
10.1016/j.immuni.2018.12.020
ISSN:
10747613