TH17 cells promote CNS inflammation by sensing danger signals via Mincle

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

doi:10.1038/s41467-022-30174-1

Back

TH17 cells promote CNS inflammation by sensing danger signals via Mincle

Journal article

Open access

Peer reviewed

TH17 cells promote CNS inflammation by sensing danger signals via Mincle

Quanri Zhang, Weiwei Liu, Han Wang, Hao Zhou, Katarzyna Bulek, Xing Chen, Cun-Jin Zhang, Junjie Zhao, Renliang Zhang, Caini Liu, …

Nature communications, Vol.13(1), pp.2406-2406

05/03/2022

DOI: 10.1038/s41467-022-30174-1

PMCID: PMC9064974

PMID: 35504893

Files and links (1)

url

https://doi.org/10.1038/s41467-022-30174-1View

Published (Version of record) Open Access

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.

Animals

Central Nervous System - metabolism

Encephalomyelitis, Autoimmune, Experimental

Glucosylceramides - metabolism

Inflammation - metabolism

Ligands

Mice

Th17 Cells

Details

Title: Subtitle: TH17 cells promote CNS inflammation by sensing danger signals via Mincle
Creators: Quanri Zhang - Cleveland Clinic
Weiwei Liu - Cleveland Clinic
Han Wang - Cleveland Clinic
Hao Zhou - Cleveland Clinic
Katarzyna Bulek - Cleveland Clinic
Xing Chen - Cleveland Clinic
Cun-Jin Zhang - Nanjing University
Junjie Zhao - Cleveland Clinic
Renliang Zhang - Cleveland Clinic
Caini Liu - Cleveland Clinic
Zizhen Kang - University of Iowa
Robert A Bermel - Cleveland Clinic
George Dubyak - Case Western Reserve University
Derek W Abbott - Case Western Reserve University
Tsan Sam Xiao - Case Western Reserve University
Laura E Nagy - Cleveland Clinic
Xiaoxia Li - Cleveland Clinic
Resource Type: Journal article
Publication Details: Nature communications, Vol.13(1), pp.2406-2406
DOI: 10.1038/s41467-022-30174-1
PMID: 35504893
PMCID: PMC9064974
NLM abbreviation: Nat Commun
eISSN: 2041-1723
Grant note: R01AA023722 / U.S. Department of Health & Human Services | National Institutes of Health (NIH)
Language: English
Date published: 05/03/2022
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984258366602771

Metrics

13 Record Views

25 Times Cited - Web of Science