New insights into the regulation of innate immunity by caspase-8

This is the authors' abstract. We don't add key points for this paper.

Caspase-8 is required for extrinsic apoptosis, but is also central for preventing a pro-inflammatory receptor interacting protein kinase (RIPK) 3-mixed lineage kinase domain-like (MLKL)-dependent cell death pathway termed necroptosis.Despite these critical cellular functions, the impact of capase-8 deletion in the myeloid cell lineage, which forms the basis for innate immune responses, has remained unclear.In a recent article in Arthritis Research & Therapy, Cuda et al. report that myeloid cell-restricted caspase-8 loss leads to a very mild RIPK3-dependent inflammatory phenotype.The presented results suggest that inflammation does not arise exclusively because of RIPK3-mediated necroptotic death but that, in the absence of caspase-8, RIPK1 and RIPK3 enhance microbiome-driven Toll-like receptor-induced pro-inflammatory cytokine production. The recent article by Cuda et al. published in ArthritisResearch & Therapy [1] characterizes abnormal immune responses in mice lacking caspase-8 in myeloid cells.This research advances our understanding of caspase-8 function in monocytes, macrophages and neutrophils, which has been difficult to study because of the embryonic lethality of whole organism caspase-8 deficiency.Caspase-8 is a cysteine-aspartic acid protease noted for its critical role in inducing death receptor and Tolllike receptor (TLR)-mediated apoptosis [2].Caspase-8 is expressed as a monomeric zymogen, which requires dimerization and cleavage to achieve full activity.