Recent advances on signaling pathways and their inhibitors in rheumatoid arthritis

Clin Immunol. 2021 Sep:230:108793. doi: 10.1016/j.clim.2021.108793. Epub 2021 Jul 6.

Abstract

Rheumatoid arthritis (RA) is characterized by systemic synovitis leading to joint destruction in which imbalances in pro-inflammatory and anti-inflammatory cytokines promote the induction of autoimmunity. Some pro-inflammatory cytokines can trigger the signaling pathways which responsible for immune-mediated inflammation in RA, and the activated signaling pathways produce pro-inflammatory cytokines, resulting in aggravation of RA. Hence, understanding of the signaling pathways and their inhibitors might be advantageous in the development of therapeutic targets and new drugs for RA. In the current review, we summarize the signaling pathways involved in the pathogenesis of RA as well as the potential role of specific inhibitors in its management. We hope this paper may serve a reference for future studies on signaling pathways implicated in the pathogenesis of RA and benefit the treatment of RA.

Keywords: JAK/STAT; MAPK; NF-κB; PI3K/AKT; Rheumatoid arthritis; SYK/BTK; Wnt; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism*
  • Cytokines / immunology
  • Cytokines / metabolism
  • Humans
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Janus Kinase Inhibitors / pharmacology
  • Janus Kinases / immunology
  • Janus Kinases / metabolism
  • MAP Kinase Signaling System / immunology
  • Models, Immunological
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / immunology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / immunology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*

Substances

  • Cytokines
  • Inflammation Mediators
  • Janus Kinase Inhibitors
  • NF-kappa B
  • Phosphoinositide-3 Kinase Inhibitors
  • Janus Kinases
  • Proto-Oncogene Proteins c-akt