Pathogen recognition receptor signaling accelerates phosphorylation-dependent degradation of IFNAR1

An ability to sense pathogens by a number of specialized cell types including the dendritic cells plays a central role in host's defenses. activation of these cells through the stimulation of the pathogen-recognition receptors induces the production of a number of cytokines including type i interferons (ifns) that mediate the diverse mechanisms of innate immunity. type i ifns interact with the type i ifn receptor,composed of ifnar1 and ifnar2 chains,to mount the host defense responses. however,at the same time,type i ifns elicit potent anti-proliferative and pro-apoptotic effects that could be detrimental for ifn-producing cells. here,we report that the activation of p38 kinase in response to pathogen-recognition receptors stimulation results in a series of phosphorylation events within the ifnar1 chain of the type i ifn receptor. this phosphorylation promotes ifnar1 ubiquitination and acceleing and the protection of activated dendritic cells from the cytotoxic effects of autocrine or paracrine type i ifn. in this paper we discuss a potential role of this mechanism in regulating the processes of innate immunity. © 2011 qian et al.