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

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Listed:
  • Yilin Wang

    (University of Glasgow)

  • Aneesah Khan

    (University of Glasgow)

  • Aristotelis Antonopoulos

    (Department of Life Sciences, Imperial College London)

  • Laura Bouché

    (Department of Life Sciences, Imperial College London)

  • Christopher D. Buckley

    (University of Birmingham, Queen Elizabeth Hospital
    University of Oxford
    Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), Glasgow, Birmingham)

  • Andrew Filer

    (University of Birmingham, Queen Elizabeth Hospital
    Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), Glasgow, Birmingham)

  • Karim Raza

    (University of Birmingham, Queen Elizabeth Hospital
    Sandwell and West Birmingham Hospitals NHS Trust)

  • Kun-Ping Li

    (Guangdong Pharmaceutical University)

  • Barbara Tolusso

    (Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), Glasgow, Birmingham
    Fondazione Policlinico Universitario A. Gemelli IRCCS)

  • Elisa Gremese

    (Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), Glasgow, Birmingham
    Fondazione Policlinico Universitario A. Gemelli IRCCS)

  • Mariola Kurowska-Stolarska

    (University of Glasgow
    Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), Glasgow, Birmingham)

  • Stefano Alivernini

    (Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), Glasgow, Birmingham
    Fondazione Policlinico Universitario A. Gemelli IRCCS
    Università Cattolica del Sacro Cuore)

  • Anne Dell

    (Department of Life Sciences, Imperial College London)

  • Stuart M. Haslam

    (Department of Life Sciences, Imperial College London)

  • Miguel A. Pineda

    (University of Glasgow
    Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), Glasgow, Birmingham)

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.

Suggested Citation

  • Yilin Wang & Aneesah Khan & Aristotelis Antonopoulos & Laura Bouché & Christopher D. Buckley & Andrew Filer & Karim Raza & Kun-Ping Li & Barbara Tolusso & Elisa Gremese & Mariola Kurowska-Stolarska & , 2021. "Loss of α2-6 sialylation promotes the transformation of synovial fibroblasts into a pro-inflammatory phenotype in arthritis," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22365-z
    DOI: 10.1038/s41467-021-22365-z
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