Details

Autor(en) / Beteiligte

• Zhang, Cun-Jin
• Wang, Chenhui
• Jiang, Meiling
• Gu, Chunfang
• Xiao, Jianxin
• Chen, Xing
• Martin, Bradley N
• Tang, Fangqiang
• Yamamoto, Erin
• Xian, Yibo
• Wang, Han
• Li, Fengling
• Sartor, R Balfour
• Smith, Howard
• Husni, M Elaine
• Shi, Fu-Dong
• Gao, Ji
• Carman, Julie
• Dongre, Ashok
• McKarns, Susan C
• Coppieters, Ken
• Jørgensen, Trine N
• Leonard, Warren J
• Li, Xiaoxia

Titel

Act1 is a negative regulator in T and B cells via direct inhibition of STAT3

Ist Teil von

• Nature communications, 2018-07, Vol.9 (1), p.2745-14, Article 2745

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. IL-23R deletion or blockade of IL-21 ameliorates SLE- and Sjögren's-like diseases in Act1 mice. Act1 deficiency results in hyperactivated follicular Th17 cells with elevated IL-21 expression, which promotes T-B cell interaction for B cell expansion and antibody production. Moreover, anti-IL-21 ameliorates the SLE- and Sjögren's-like diseases in Act1-deficient mice. Thus, IL-21 blocking antibody might be an effective therapy for treating SLE- and Sjögren's-like syndrome in patients containing Act1 mutation.