Enhancing the effectiveness of immunotherapy in rheumatoid arthritis by delaying immunosenescence triggered by fibroblast-like synoviocytes

J Orthop Surg Res. 2025 Jan 23;20(1):87. doi: 10.1186/s13018-025-05473-0.

Abstract

Rheumatoid arthritis (RA) is a prevalent autoimmune disorder primarily targeting the diarthrodial joints. During the progression of RA, fibroblast-like synoviocytes (FLSs) exhibit tumor-like behavior, including increased proliferation, inflammation mediation, and aggressive phenotypes, leading to bone erosion. Additionally, T cells in RA acquire pro-inflammatory characteristics, exacerbating the inflammatory environment in affected joints and associated tissues. Notably, senescent T cells contribute to inflammation, further accelerating the disease process. Metabolic changes in rheumatoid FLSs not only maintain their tumor-like properties but also trigger inflammatory cascades, particularly affecting T lymphocytes. This review examines the molecular alterations in RA FLSs in the context of systemic immune aging, with a focus on thymic insufficiency-associated T cell senescence, and explores potential therapeutic avenues.

Keywords: Fibroblast-like synoviocytes; Immunosenescence; Metabolites/cytokines; Rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Arthritis, Rheumatoid* / immunology
  • Arthritis, Rheumatoid* / therapy
  • Cellular Senescence / immunology
  • Fibroblasts* / immunology
  • Humans
  • Immunosenescence*
  • Immunotherapy* / methods
  • Synoviocytes* / immunology
  • Synoviocytes* / metabolism
  • T-Lymphocytes / immunology