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DOI | 10.1038/s41467-018-07076-2 |
Act1 is a negative regulator in T and B cells via direct inhibition of STAT3 | |
Zhang, Cun-Jin1,2,3; Wang, Chenhui1,4,5; Jiang, Meiling1,6,7; Gu, Chunfang1; Xiao, Jianxin1; Chen, Xing1; Martin, Bradley N.1; Tang, Fangqiang1; Yamamoto, Erin1; Xian, Yibo1; Wang, Han1; Li, Fengling8,9; Sartor, R. Balfour8,9,10; Smith, Howard11; Husni, M. Elaine11; Shi, Fu-Dong2,3,12; Gao, Ji13; Carman, Julie13; Dongre, Ashok13; McKarns, Susan C.14,15; Coppieters, Ken16; Jorgensen, Trine N.1; Leonard, Warren J.17,18; Li, Xiaoxia1 | |
2018-07-16 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Peoples R China; Denmark |
英文摘要 | Although Act1 (adaptor for IL-17 receptors) is necessary for IL-17-mediated inflammatory responses, Act1- (but not ll17ra-, ll17rc-, or ll17rb-) deficient mice develop spontaneous SLE-and Sjogren'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 ll17ra-, ll17rc-, or II17rb) results in hyper IL23- and IL-21-induced STAT3 activation in T and B cells, respectively. IL-23R deletion or blockade of IL-21 ameliorates SLE- and Sjogren'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, antiIL-21 ameliorates the SLE- and Sjogren's-like diseases in Act1-deficient mice. Thus, IL-21 blocking antibody might be an effective therapy for treating SLE- and Sjogren's-like syndrome in patients containing Act1 mutation. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000438683800003 |
WOS关键词 | SYSTEMIC-LUPUS-ERYTHEMATOSUS ; FOLLICULAR HELPER-CELLS ; MYASTHENIA-GRAVIS ; SJOGRENS-SYNDROME ; ADAPTER ACT1 ; DISEASE ; IL-21 ; SUSCEPTIBILITY ; INFLAMMATION ; PATHOGENESIS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204065 |
专题 | 资源环境科学 |
作者单位 | 1.Cleveland Clin, Dept Inflammat & Immun, Lerner Res Inst, Cleveland, OH 44106 USA; 2.Tianjin Med Univ Gen Hosp, Dept Neurol, Tianjin Neurol Inst, Tianjin 300051, Peoples R China; 3.Capital Med Univ, Beijing Tiantan Hosp, Ctr Neuroinflammat, Beijing 100050, Peoples R China; 4.Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Key Lab Mol Biophys, Minist Educ, Wuhan 430074, Hubei, Peoples R China; 5.Wuhan Inst Biotechnol, Wuhan 430200, Hubei, Peoples R China; 6.Chinese Acad Med Sci, Inst Radiat Med, Tianjin 300192, Peoples R China; 7.Peking Union Med Coll, Tianjin 300192, Peoples R China; 8.Univ N Carolina, Natl Gnotobiot Rodent Resource Ctr, Dept Med, Chapel Hill, NC 27599 USA; 9.Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC 27599 USA; 10.Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA; 11.Cleveland Clin, Dept Rheumatol & Immunol Dis, Cleveland, OH 44106 USA; 12.St Josephs Hosp, Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA; 13.Bristol Myers Squibb, Discovery Biol, Princeton, NJ 08540 USA; 14.Univ Missouri, Sch Med, Dept Surg, Columbia, MO 65212 USA; 15.Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA; 16.Novo Nordisk AS, Type Diabet Ctr 1, DK-2860 Soborg, Denmark; 17.NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA; 18.NHLBI, Immunol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA |
推荐引用方式 GB/T 7714 | Zhang, Cun-Jin,Wang, Chenhui,Jiang, Meiling,et al. Act1 is a negative regulator in T and B cells via direct inhibition of STAT3[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Zhang, Cun-Jin.,Wang, Chenhui.,Jiang, Meiling.,Gu, Chunfang.,Xiao, Jianxin.,...&Li, Xiaoxia.(2018).Act1 is a negative regulator in T and B cells via direct inhibition of STAT3.NATURE COMMUNICATIONS,9. |
MLA | Zhang, Cun-Jin,et al."Act1 is a negative regulator in T and B cells via direct inhibition of STAT3".NATURE COMMUNICATIONS 9(2018). |
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