Loss of α2-6 sialylation promotes the transformation of synovial fibroblasts into a pro-inflammatory phenotype in arthritis.
Author
Wang, YilinKhan, Aneesah
Antonopoulos, Aristotelis
Bouché, Laura
Buckley, Christopher D
Filer, Andrew
Raza, Karim
Li, Kun-Ping
Tolusso, Barbara
Gremese, Elisa
Kurowska-Stolarska, Mariola
Alivernini, Stefano
Dell, Anne
Haslam, Stuart M
Pineda, Miguel A
Affiliation
University of Glasgow; Imperial College London; University of Birmingham; Sandwell and West Birmingham NHS TrustPublication date
2021-04-20Subject
Rheumatology
Metadata
Show full item recordAbstract
In healthy joints, synovial fibroblasts (SFs) provide the microenvironment required to mediate homeostasis, but these cells adopt a pathological function in rheumatoid arthritis (RA). Carbohydrates (glycans) on cell surfaces are fundamental regulators of the interactions between stromal and immune cells, but little is known about the role of the SF glycome in joint inflammation. Here we study stromal guided pathophysiology by mapping SFs glycosylation pathways. Combining transcriptomic and glycomic analysis, we show that transformation of fibroblasts into pro-inflammatory cells is associated with glycan remodeling, a process that involves TNF-dependent inhibition of the glycosyltransferase ST6Gal1 and α2-6 sialylation. SF sialylation correlates with distinct functional subsets in murine experimental arthritis and remission stages in human RA. We propose that pro-inflammatory cytokines remodel the SF-glycome, converting the synovium into an under-sialylated and highly pro-inflammatory microenvironment. These results highlight the importance of glycosylation in stromal immunology and joint inflammation.Citation
Wang Y, Khan A, Antonopoulos A, Bouché L, Buckley CD, Filer A, Raza K, Li KP, Tolusso B, Gremese E, Kurowska-Stolarska M, Alivernini S, Dell A, Haslam SM, Pineda MA. Loss of α2-6 sialylation promotes the transformation of synovial fibroblasts into a pro-inflammatory phenotype in arthritis. Nat Commun. 2021 Apr 20;12(1):2343.Type
ArticlePMID
33879788Journal
Nature CommunicationsPublisher
Nature Researchae974a485f413a2113503eed53cd6c53
10.1038/s41467-021-22365-z