Dying cells fan the flames of inflammation

Inflammatory processes that recruit leukocytes to injured or infected tissues are crucial for tissue repair and the elimination of pathogens. However, excessive or chronic inflammation promotes tissue damage and disease, as in arthritis, atherosclerosis, inflammatory bowel disease, and COVID-19. Intracellular constituents released from dying cells are among the stimuli that trigger proinflammatory gene expression programs in innate immune cells. We explore how programmed cell death mechanisms-apoptosis, necroptosis, and pyroptosis-may contribute to inflammatory disease. We discuss inhibition of cell death as a potential therapeutic strategy, focusing on the targets RIPK1 (receptor interacting serine/threonine kinase 1), NLRP3 (NLR family pyrin domain containing 3), and GSDMD (gasdermin D) as important mediators of lytic cell death. We also consider the potential benefits of limiting membrane rupture rather than cell death by targeting NINJ1.

Automated summary

Inflammatory processes are crucial for tissue repair and pathogen elimination, but excessive or chronic inflammation can lead to diseases such as arthritis and COVID-19. Different cell death mechanisms like apoptosis, necroptosis, and pyroptosis may contribute to inflammatory diseases. Inhibiting cell death and targeting specific mediators of lytic cell death could be potential therapeutic strategies.