Role of necroptosis in infection‐related, immune‐mediated, and autoimmune skin diseases

Abstract Regulated necrosis, also termed necroptosis, is another programmed cell death depending on a unique molecular pathway that does not overlap with apoptosis. Tumor necrosis factor and Toll‐like receptor family members, interferon, and other mediators are the factors that mainly cause necroptosis. Activating necroptosis by ligands of death receptors requires the kinase activity of receptor‐interacting proteins 1 and 3, and a mixed lineage kinase domain‐like protein, which is a critical downstream mediator of necroptosis. Increasing evidence has revealed that necroptosis does not only involve physiological regulation but also the occurrence, development, and prognosis of certain diseases, such as septicemia, neurodegenerative diseases, and ischemic–reperfusion injury. Many excellent documented systematic discussions of necroptosis and its role in various skin diseases. In this review, we summarize the molecular mechanism of necroptosis, as well as the current knowledge on the contribution of necroptosis, in infection‐related, immune‐mediated, autoimmune skin diseases, and malignant skin tumors.