Involvement of IKKα in STAT1 phosphorylation in antiviral signaling

• Published in: The Journal of immunology (1950) 2017-05, Vol.198 (1_Supplement), p.129-129.20
• Main Authors: Matsumiya, Tomoh, Xing, Fei, Shiba, Yuko, Hayakari, Ryo, Yoshida, Hidemi, Imaizumi, Tadaatsu
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.198.Supp.129.20

RIG-I-like receptors (RLRs) sense non-self RNA, inducing type I IFNs. Type I IFN promotes the expression of IFN-stimulated genes (ISGs), which requires the activation of STAT1. We previously reported that dsRNA induced STAT1 phosphorylation via a type I IFN-independent pathway in addition to the well-known type I IFN-dependent pathway. IKKα is involved in antiviral signaling induced by dsRNA in the RLR-mediated antiviral signaling; however, its role remains uncertain. In this study, we investigated the role of IKKα in RLR signaling, which is essential for antiviral innate immune responses in non-professional antigen-presenting cells, such as epithelial cells. Silencing of IKKα markedly decreased the level of IFN-β and STAT1 phosphorylation in response to dsRNA. However, the inhibition of IKKα did not alter the RLR signaling-mediated dimerization of IRF3 or activation of NFκB. These results suggest a non-canonical role of IKKα in RLR signaling. In addition, STAT1 phosphorylation was inhibited by IKKα knockdown in IFNAR-deficient cells. These results suggest that the dual regulation of STAT1 by IKKα in the RLR-mediated antiviral signaling.