JAK-STAT signaling pathway in non-infectious uveitis

Biochem Pharmacol. 2022 Oct:204:115236. doi: 10.1016/j.bcp.2022.115236. Epub 2022 Aug 27.

Abstract

Non-infectious uveitis (NIU) refers to various intraocular inflammatory disorders responsible for severe visual loss. Cytokines participate in the regulation of ocular homeostasis and NIU pathological processes. Cytokine receptors transmit signals by activating Janus kinase (JAK) and signal transducer and activator of transcription (STAT) proteins. Increasing evidence from human NIU and experimental models reveals the involvement of the JAK-STAT signaling pathway in NIU pathogenesis. Several small-molecule drugs that potentially inhibit multiple cytokine-dependent pathways are under investigation for treating autoimmune diseases, implicating possible applications for NIU treatment. This review summarizes the current understanding of the diverse roles of the JAK-STAT signaling pathway in ocular homeostasis and NIU pathology, providing a rationale for targeting JAKs and STATs for NIU treatment. Moreover, available evidence for the safety and efficacy of JAK inhibitors for refractory uveitis and potential approaches for treatment optimization are discussed.

Keywords: Cytokine; Janus kinase; Non-infectious uveitis; Signal transducer and activator of transcription.

Publication types

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

MeSH terms

  • Cytokines / metabolism
  • Humans
  • Janus Kinase Inhibitors* / pharmacology
  • Janus Kinase Inhibitors* / therapeutic use
  • Janus Kinases
  • Receptors, Cytokine / metabolism
  • STAT Transcription Factors / metabolism
  • Signal Transduction / physiology
  • Uveitis* / drug therapy

Substances

  • Cytokines
  • Janus Kinase Inhibitors
  • Receptors, Cytokine
  • STAT Transcription Factors
  • Janus Kinases