RIP-roaring inflammation: RIPK1 and RIPK3 driven NLRP3 inflammasome activation and autoinflammatory disease

Mary Speir, Kate E. Lawlor

Research output: Contribution to journalReview ArticleResearchpeer-review

16 Citations (Scopus)


Autoinflammatory syndromes comprise a spectrum of clinical disorders characterised by recurrent, inflammatory episodes, many of which result from the release of the pro-inflammatory cytokine, interleukin-1β (IL-1β). Inflammation and programmed cell death are tightly linked, and lytic forms of cell death, such as necroptosis and pyroptosis, are considered to be inflammatory due to the release of damage-associated molecular patterns (DAMPs). In contrast, apoptosis is traditionally regarded as immunologically silent. Recent studies, however, have uncovered a high degree of crosstalk between cell death and inflammatory signalling pathways, and effectively consolidated them into one interconnected network that converges on NLRP3 inflammasome-mediated activation of IL-1β. The receptor-interacting protein kinases (RIPK) 1 and 3 are central to this network, as highlighted by the fact that mutations in genes encoding repressors of RIPK1 and/or RIPK3 activity can lead to heightened inflammation, particularly via NLRP3 inflammasome activation. In this review, we give an overview of extrinsic cell death and inflammatory signalling pathways, and then highlight the growing number of autoinflammatory diseases that are associated with aberrant cell death and inflammasome activation.

Original languageEnglish
Pages (from-to)114-124
Number of pages11
JournalSeminars in Cell and Developmental Biology
Issue numberS1
Publication statusPublished - Jan 2021


  • Autoinflammation
  • Cell death
  • Interleukin-1
  • NLRP3 inflammasome
  • RIP kinases
  • Tumour necrosis factor

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