TH17 Cells Promote CNS Inflammation by Sensing Danger Signals Via Mincle

Overview

Journal Nat Commun

Specialty Biology

Date 2022 May 3

PMID 35504893

Authors

Quanri Zhang

Weiwei Liu

Han Wang

Hao Zhou

Katarzyna Bulek

Xing Chen

Cun-Jin Zhang

Junjie Zhao

Renliang Zhang

Caini Liu

Zizhen Kang

Robert A Bermel

George Dubyak

Derek W Abbott

Tsan Sam Xiao

Laura E Nagy

Xiaoxia Li

Affiliations

Soon will be listed here.

Abstract

The C-type lectin receptor Mincle is known for its important role in innate immune cells in recognizing pathogen and damage associated molecular patterns. Here we report a T cell-intrinsic role for Mincle in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Genomic deletion of Mincle in T cells impairs TH17, but not TH1 cell-mediated EAE, in alignment with significantly higher expression of Mincle in TH17 cells than in TH1 cells. Mechanistically, dying cells release β-glucosylceramide during inflammation, which serves as natural ligand for Mincle. Ligand engagement induces activation of the ASC-NLRP3 inflammasome, which leads to Caspase8-dependent IL-1β production and consequentially TH17 cell proliferation via an autocrine regulatory loop. Chemical inhibition of β-glucosylceramide synthesis greatly reduces inflammatory CD4+ T cells in the central nervous system and inhibits EAE progression in mice. Taken together, this study indicates that sensing of danger signals by Mincle on TH17 cells plays a critical role in promoting CNS inflammation.

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