粘膜免疫学研究杂志

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Ripk1 Mediated Regulation Of Zbp1 Activation: An Emerging Regulatory Mechanism In Cell Death, Inflammation And Development

Sannula Kesavardhana

Regulated cell death and inflammation are critical in orchestrating cellular homeostasis, development and host defense responses. The RIP-homotypic interaction motif (RHIM) containing proteins, RIPK1, RIPK3, TRIF and ZBP1, play an important role in triggering cell death and inflammation via assembling signaling complexes. RIPK1 and ZBP1 independently promote RIPK3-MLKL mediated inflammatory cell death called necroptosis. The RIPK1-RIPK3 signaling axis is well described in the death-receptor, TLR and other innate immune receptor signaling pathways for triggering necroptosis and in embryonic development. ZBP1 is a Z-nucleic acid sensor that promotes virus induced RIPK3 activation and necroptosis. This review focuses on recent findings that led to the identification of RIPK1 function in counteracting ZBP1 activation in physiological conditions and its importance in defining new intracellular mechanisms of cell death and inflammation.