Fibroblast pathology in inflammatory joint disease

Lucy-Jayne Marsh, Samuel Kemble, Patricia Reis Nisa, Ruchir Singh, Adam P Croft

Research output: Contribution to journalReview articlepeer-review

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Abstract

Rheumatoid arthritis is an immune-mediated inflammatory disease in which fibroblasts contribute to both joint damage and inflammation. Fibroblasts are a major cell constituent of the lining of the joint cavity called the synovial membrane. Under resting conditions, fibroblasts have an important role in maintaining joint homeostasis, producing extracellular matrix and joint lubricants. In contrast, during joint inflammation, fibroblasts contribute to disease pathology by producing pathogenic levels of inflammatory mediators that drive the recruitment and retention of inflammatory cells within the joint. Recent advances in single-cell profiling techniques have transformed our ability to examine fibroblast biology, leading to the identification of specific fibroblast subsets, defining a previously underappreciated heterogeneity of disease-associated fibroblast populations. These studies are challenging the previously held dogma that fibroblasts are homogeneous and are providing unique insights into their role in inflammatory joint pathology. In this review, we discuss the recent advances in our understanding of how fibroblast heterogeneity contributes to joint pathology in rheumatoid arthritis. Finally, we address how these insights could lead to the development of novel therapies that directly target selective populations of fibroblasts in the future.

Original languageEnglish
Pages (from-to)163-183
JournalImmunological Reviews
Volume302
Issue number1
Early online date6 Jun 2021
DOIs
Publication statusE-pub ahead of print - 6 Jun 2021

Bibliographical note

© 2021 The Authors. Immunological Reviews published by John Wiley & Sons Ltd.

Keywords

  • fibroblasts
  • inflammation
  • inflammatory disease
  • rheumatoid arthritis
  • single-cell transcriptomics
  • synovium

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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