Cun-Jin Zhang, Chenhui Wang, Meiling Jiang, Chunfang Gu, Jianxin Xiao, Xing Chen, Bradley N Martin, Fangqiang Tang, Erin Yamamoto, Yibo Xian, Han Wang, Fengling Li, R Balfour Sartor, Howard Smith, M Elaine Husni, Fu-Dong Shi, Ji Gao, Julie Carman, Ashok Dongre, Susan C McKarns, Ken Coppieters, Trine N Jørgensen, Warren J Leonard, Xiaoxia Li
Although Act1 (adaptor for IL-17 receptors) is necessary for IL-17-mediated inflammatory responses, Act1- (but not Il17ra-, Il17rc-, or Il17rb-) deficient mice develop spontaneous SLE- and Sjögren's-like diseases. Here, we show that Act1 functions as a negative regulator in T and B cells via direct inhibition of STAT3. Mass spectrometry analysis detected an Act1-STAT3 complex, deficiency of Act1 (but not Il17ra-, Il17rc-, or Il17rb) results in hyper IL-23- and IL-21-induced STAT3 activation in T and B cells, respectively...
July 16, 2018: Nature Communications