Novel roles for caspase-8 in IL-1β and inflammasome regulation

Am J Pathol. 2015 Jan;185(1):17-25. doi: 10.1016/j.ajpath.2014.08.025. Epub 2014 Nov 1.


Caspase-8 is an initiator and apical activator caspase that plays a central role in apoptosis. Caspase-8-deficient mice are embryonic lethal, which makes study of caspase-8 in primary immune cells difficult. Recent advances have rescued caspase-8-deficient mice by crossing them to mice deficient in receptor-interacting serine-threonine kinase 3 (RIPK3). These genetic tools have made it possible to study the role of caspase-8 in vivo and in primary immune cells. Several recent studies have identified novel roles for caspase-8 in modulating IL-1β and inflammation, showing that caspase-8 directly regulates IL-1β independent of inflammasomes or indirectly through the regulation of inflammasomes, depending on the stimulus or stimuli that initiate the signaling cascade. Here, we address recent findings on caspase-8 and its role in modulating IL-1β and inflammation.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmunity
  • Caspase 8 / physiology*
  • Endoplasmic Reticulum Stress
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Inflammasomes / immunology*
  • Inflammation / immunology*
  • Interleukin-1beta / physiology*
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Protein Structure, Tertiary
  • Receptor-Interacting Protein Serine-Threonine Kinases / genetics
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction


  • Inflammasomes
  • Interleukin-1beta
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ripk3 protein, mouse
  • CASP8 protein, human
  • Casp8 protein, mouse
  • Caspase 8