Loss of α2-6 sialylation promotes the transformation of synovial fibroblasts into a pro-inflammatory phenotype in arthritis.
Wang, Yilin Khan, Aneesah Antonopoulos, Aristotelis Bouché, Laura Buckley, Christopher D Filer, Andrew Raza, Karim Li, Kun-Ping Tolusso, Barbara Gremese, Elisa
Wang, Yilin
Khan, Aneesah
Antonopoulos, Aristotelis
Bouché, Laura
Buckley, Christopher D
Filer, Andrew
Raza, Karim
Li, Kun-Ping
Tolusso, Barbara
Gremese, Elisa
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Affiliation
University of Glasgow; Imperial College London; University of Birmingham; Sandwell and West Birmingham NHS Trust
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Publication date
2021-04-20
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Abstract
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.
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Article