Loss of α2-6 sialylation promotes the transformation of synovial fibroblasts into a pro-inflammatory phenotype in arthritis

Elisa Gremese, Stefano Alivernini, Barbara Tolusso, Yilin Wang, Aneesah Khan, Aristotelis Antonopoulos, Laura Bouché, Christopher D. Buckley, Andrew Filer, Karim Raza, Kun-Ping Li, Mariola Kurowska-Stolarska, Anne Dell, Stuart M. Haslam, Miguel A. Pineda

Risultato della ricerca: Contributo in rivistaArticolo in rivista

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.
Lingua originaleEnglish
pagine (da-a)2343-N/A
RivistaNature Communications
Volume12
DOI
Stato di pubblicazionePubblicato - 2021

Keywords

  • Animals
  • Arthritis, Experimental
  • Arthritis, Rheumatoid
  • Cell Line
  • Cytokines
  • Down-Regulation
  • Fibroblasts
  • Glycosylation
  • Humans
  • Inflammation
  • Male
  • Metabolic Networks and Pathways
  • Mice
  • Mice, Inbred DBA
  • Phenotype
  • RNA-Seq
  • Sialic Acids
  • Sialyltransferases
  • Synovial Membrane
  • Transcriptome

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