Consequences of dendritic cell necroptosis on the immune system (P5105)

Abstract

Abstract Dendritic cells (DCs) are essential in eliciting protective responses against pathogens, thus appropriate DC functions are essential in maintaining proper immune responses. The maintenance of DC homeostasis relies heavily on apoptosis to prevent disease development, and inhibition of DC apoptosis has been previously reported to induce systemic autoimmune disease. Fas-associated death domain-containing protein (FADD) is a critical adaptor protein that interacts with caspase-8 to transmit apoptotic signals downstream of the tumor necrosis factor family of death receptors. More recently, an alternative form of cell death, termed necroptosis, was reported to be downstream of the death receptors. Necroptosis is caspase-independent and requires the kinase activities of receptor interacting serine/threonine protein kinase 1 (RIP1) and RIP3. To investigate the role of FADD in DC death, DC-specific FADD conditional knockout mice were generated. Interestingly, these mice developed an inflammatory phenotype. We further elucidated the cause of inflammation by crossing the mice to RIP3-/-, MyD88-/- and MyD88flox/flox mutant mice. Our recent findings based on the analysis of these mice will be discussed.