Targeting rip kinases in chronic inflammatory disease

Mary Speir, Tirta M. Djajawi, Stephanie A. Conos, Hazel Tye, Kate E. Lawlor

Research output: Contribution to journalReview ArticleResearchpeer-review

9 Citations (Scopus)

Abstract

Chronic inflammatory disorders are characterised by aberrant and exaggerated inflammatory immune cell responses. Modes of extrinsic cell death, apoptosis and necroptosis, have now been shown to be potent drivers of deleterious inflammation, and mutations in core repressors of these pathways underlie many autoinflammatory disorders. The receptor-interacting protein (RIP) kinases, RIPK1 and RIPK3, are integral players in extrinsic cell death signalling by regulating the production of pro-inflammatory cytokines, such as tumour necrosis factor (TNF), and coordinating the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, which underpin patholog-ical inflammation in numerous chronic inflammatory disorders. In this review, we firstly give an overview of the inflammatory cell death pathways regulated by RIPK1 and RIPK3. We then discuss how dysregulated signalling along these pathways can contribute to chronic inflammatory disorders of the joints, skin, and gastrointestinal tract, and discuss the emerging evidence for targeting these RIP kinases in the clinic.

Original languageEnglish
Article number646
Number of pages22
JournalBiomolecules
Volume11
Issue number5
DOIs
Publication statusPublished - May 2021

Keywords

  • Apoptosis
  • Chronic inflammatory disease
  • Interleukin-1
  • Necroptosis
  • RIP kinases
  • Tumour necrosis factor

Cite this