| First Author | Zhang Q | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 2406 |
| PubMed ID | 35504893 | Mgi Jnum | J:354863 |
| Mgi Id | MGI:7275754 | Doi | 10.1038/s41467-022-30174-1 |
| Citation | Zhang Q, et al. (2022) TH17 cells promote CNS inflammation by sensing danger signals via Mincle. Nat Commun 13(1):2406 |
| abstractText | 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 beta-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-1beta production and consequentially TH17 cell proliferation via an autocrine regulatory loop. Chemical inhibition of beta-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. |
