Frontiers in Immunology (Jan 2022)

Interleukin 27 Signaling in Rheumatoid Arthritis Patients: Good or Evil?

  • Liang Han,
  • Zhe Chen,
  • Kun Yu,
  • Jiahui Yan,
  • Tingting Li,
  • Xin Ba,
  • Weiji Lin,
  • Yao Huang,
  • Pan Shen,
  • Ying Huang,
  • Kai Qin,
  • Yinhong Geng,
  • Yafei Liu,
  • Yu Wang,
  • Shenghao Tu

DOI
https://doi.org/10.3389/fimmu.2021.787252
Journal volume & issue
Vol. 12

Abstract

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The occurrence and development of rheumatoid arthritis (RA) is regulated by numerous cytokines. Interleukin 27 (IL-27) is a soluble cytokine that exerts biological effects by regulating the Janus tyrosine kinase (JAK)/signal transducer and activator of the transcription (STAT) signaling pathway via the IL-27 receptor. IL-27 is known for its pleiotropic roles in modulating inflammatory responses. Previous studies found that IL-27 levels are elevated in RA blood, synovial fluid, and rheumatoid nodules. Cellular and animal experiments indicated that IL-27 exerts multiple regulatory functions in RA patients via different mechanisms. IL-27 inhibits ectopic-like structure (ELS) formation and CD4+ T helper type 2 (Th2) cell, CD4+ T helper type 17 (Th17) cell, and osteoclast differentiation in RA, contributing to alleviating RA. However, IL-27 promotes Th1 cell differentiation, which may exacerbate RA synovitis. Moreover, IL-27 also acts on RA synovial fibroblasts (RA-FLSs) and regulatory T cells (Tregs), but some of its functions are unclear. There is currently insufficient evidence to determine whether IL-27 promotes or relieves RA. Targeting IL-27 signaling in RA treatment should be deliberate based on current knowledge.

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