Roles of necroptosis in immune responses

Abstract

Cell survival and cell death should be well regulated in an orchestrated way for cell proliferation, differentiation, and development in multicellular organism. A variety of physiological outcomes in vertebrate is dependent on cell death modality in response to infectious pathogens and functionally damaged cells. Physiological and pathological roles of cell death are often addressed to describe normal and disease state. Particularly, immune responses can be affected from cell death modes of host cells and various immune-associated cells. Immunogenic cell death occurs in either an accidental or a regulated way could elicit the immune responses. Representatively, apoptosis and necroptosis are involved in homeostasis of immune reaction. So far, apoptosis in immune system has been well defined, acting as deletion of self-recognizing immune cells and cytotoxic killing. However, it has been a growing body of evidence that alternative programmed cell death necroptosis could be involved in immune surveillance, although its underlying mechanism remains elusive. Therefore, necroptosis or programmed necrosis will be emphasized as a regulator of immunity. With immunological role of necroptosis, unmasking of necroptosis and its associated signaling pathway are also dealt in this review. complex II consisting of RIP1, RIP3, FADD, pro-caspase-8. Then, activated RIP3 recruits MLKL to induce the necrotic process. Based on necroptotic signaling pathway, some chemicals have been identified as pharmacological inhibitors of the necroptotic proteins. RIP1, RIP3 or MLKL can be specifically modulated by chemical inhibitors indicated.