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 () and Xiaoxia Li ()
Additional contact information
Quanri Zhang: Cleveland Clinic, Lerner Research Institute
Weiwei Liu: Cleveland Clinic, Lerner Research Institute
Han Wang: Cleveland Clinic, Lerner Research Institute
Hao Zhou: Cleveland Clinic, Lerner Research Institute
Katarzyna Bulek: Cleveland Clinic, Lerner Research Institute
Xing Chen: Cleveland Clinic, Lerner Research Institute
Cun-Jin Zhang: Nanjing Drum Tower Hospital, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University
Junjie Zhao: Cleveland Clinic, Lerner Research Institute
Renliang Zhang: Lerner Research Institute
Caini Liu: Cleveland Clinic, Lerner Research Institute
Zizhen Kang: University of Iowa
Robert A. Bermel: Mellen Center for Multiple Sclerosis, Cleveland Clinic
George Dubyak: University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine
Derek W. Abbott: Case Western Reserve University
Tsan Sam Xiao: Case Western Reserve University
Laura E. Nagy: Cleveland Clinic, Lerner Research Institute
Xiaoxia Li: Cleveland Clinic, Lerner Research Institute

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-30174-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30174-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-30174-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().