TBK1 as a regulator of autoimmunity and antitumor immunity

摘要

TANK-binding kinase 1(TBK1)and its homolog IκB kinase(IKK)epsilon(IKKε,also known as IKKi)are serine/threonine kinases that are well known for their functions to mediate type I interferon(IFN-I)induction in antiviral innate immune responses.1 Various microbial components,or pathogen associated molecular patterns(PAMPs),activate TBK1 and IKKεvia stimulating pattern-recognition receptors(PRRs)in innate immune cells.Upon activation,TBK1 or IKKε(hereafter called TBK1/IKKε)phosphorylates the transcription factors IRF3 and IRF7 to trigger their dimerization and nuclear translocation,leading to induction of IFN-I gene expression.1,2 In this innate immune signaling pathway,TBK1 and IKKεdisplay functional redundancies,although TBK1 seems to be more crucial than IKKε.3,4 It is increasingly clear that the function of TBK1 and IKKεis beyond the regulation of antiviral innate immunity.