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- Title
TH17 cells promote CNS inflammation by sensing danger signals via Mincle.
- Authors
Zhang, Quanri; Liu, Weiwei; Wang, Han; Zhou, Hao; Bulek, Katarzyna; Chen, Xing; Zhang, Cun-Jin; Zhao, Junjie; Zhang, Renliang; Liu, Caini; Kang, Zizhen; Bermel, Robert A.; Dubyak, George; Abbott, Derek W.; Xiao, Tsan Sam; Nagy, Laura E.; Li, Xiaoxia
- 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. Mincle is a pattern recognition receptor that senses danger signals in innate immune cells. Here authors show in an experimental autoimmune encephalomyelitis mouse model that tissue damage triggers Mincle signaling on inflammatory helper T cells, leading to inflammasome-mediated IL-1β production and reinforced inflammation.
- Subjects
T helper cells; TH1 cells; PATTERN perception receptors; CENTRAL nervous system; INFLAMMATION
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-30174-1