Necroptotic movers and shakers: cell types, inflammatory drivers and diseases

• Published in: Current opinion in immunology Vol. 68; pp. 83 - 97
• Main Authors: Weir, Ashley, Hughes, Sebastian, Rashidi, Maryam, Hildebrand, Joanne M, Vince, James E
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2021
• ISSN: 0952-7915; 1879-0372
• DOI: 10.1016/j.coi.2020.09.008

•MLKL has diverse cellular functions to increase necroptotic-associated inflammation.•Necroptotic cells release molecules distinct from those released by apoptosis.•Humans lacking anti-necroptotic components suffer from autoinflammatory disease.•Necroptosis can drive inflammation via activation of the NLRP3 inflammasome.•Necroptosis of distinct cell types can cause skin, liver, kidney and intestinal diseases. The necroptotic cell death pathway has received significant attention for its ability to trigger inflammatory responses and its potential involvement in related conditions. Recent insights into the essential membrane damaging necroptotic pseudokinase effector, Mixed lineage kinase domain like (MLKL), have revealed a number of diverse MLKL functions that contribute to the inflammatory nature of necroptosis. Here we review distinct MLKL signalling roles and document the immunogenic molecules released by necroptosis. We discuss specific in vivo MLKL-driven responses, the activation of inflammasome complexes and innate lymphoid cells, which have been documented to drive disease. Finally, we list necroptotic competent cell types and their involvement in MLKL-driven cell death-associated and inflammatory-associated conditions.