Why Do We Need JAK Inhibitors in Systemic Lupus Erythematosus?

Int J Mol Sci. 2022 Oct 4;23(19):11788. doi: 10.3390/ijms231911788.

Abstract

Systemic lupus erythematosus (SLE) is a chronic, multifactorial autoimmune disease with complex pathogenesis characterized by the imbalance of pro-inflammatory and anti-inflammatory cytokines. Janus kinases (JAKs), intracellular non-receptor tyrosine kinases, are essential for signal pathways of many cytokines. The JAK signal transducers and activators of transcription (STAT) pathways consist of four JAK kinases and seven STATs family members. The dysregulation of JAK-STAT pathways represents an important process in the pathogenesis of SLE. Thus, the use of therapies that target specific signaling pathways would be a challenge in SLE. It is well known that JAK inhibitors have real potential for the treatment of rheumatic diseases, but their efficacy in the treatment of SLE remains to be determined. JAK inhibitors are currently being investigated in phase II and III trials and are considered to become the next stage in SLE therapy. In this review, we report the current data regarding the efficacy of JAK inhibitors in SLE. The development of clinically useful kinase inhibitors might improve upon traditional therapeutic strategies.

Keywords: JAK inhibitor; Janus kinases; cytokines; systemic lupus erythematosus.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Cytokines / metabolism
  • Humans
  • Janus Kinase Inhibitors* / pharmacology
  • Janus Kinase Inhibitors* / therapeutic use
  • Janus Kinases / metabolism
  • Lupus Erythematosus, Systemic* / drug therapy
  • STAT Transcription Factors / metabolism
  • Tyrosine

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Janus Kinase Inhibitors
  • STAT Transcription Factors
  • Tyrosine
  • Janus Kinases

Grants and funding

This research received no external funding.