娟 刘;Chaofeng Han;Bin Xie;Yue Wu;Shuxun Liu;Kun Chen;Meng Xia;Yuan Zhang;Lijun Song;Zhiqing Li;Ting Zhang;Feng Ma;Qingqing Wang;Jianli Wang;Kejing Deng;Yuan Zhuang;Xiaohui Wu;Yizhi Yu;田 许;雪涛 曹
Second Military Medical University;Chinese Academy of Medical Sciences;Zhejiang University;Fudan University
发表时间:2014-7
期 刊:Nature Immunology
语 言:English
U R L: http://www.scopus.com/inward/record.url?scp=84903556575&partnerID=8YFLogxK
Excessive activation of dendritic cells (DCs) leads to the development of autoimmune and inflammatory diseases, which has prompted a search for regulators of DC activation. Here we report that Rhbdd3, a member of the rhomboid family of proteases, suppressed the activation of DCs and production of interleukin 6 (IL-6) triggered by Toll-like receptors (TLRs). Rhbdd3-deficient mice spontaneously developed autoimmune diseases characterized by an increased abundance of the TH17 subset of helper T cells and decreased number of regulatory T cells due to the increase in IL-6 from DCs. Rhbdd3 directly bound to Lys27 (K27)-linked polyubiquitin chains on Lys302 of the modulator NEMO (IKKυ 3) via the ubiquitin-binding-association (UBA) domain in endosomes. Rhbdd3 further recruited the deubiquitinase A20 via K27-linked polyubiquitin chains on Lys268 to inhibit K63-linked polyubiquitination of NEMO and thus suppressed activation of the transcription factor NF-κB in DCs. Our data identify Rhbdd3 as a critical regulator of DC activation and indicate K27-linked polyubiquitination is a potent ubiquitin-linked pattern involved in the control of autoimmunity.
Scopus度量
年份 | CiteScore | SJR | SNIP |
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1996 | |||
1997 | |||
1998 | |||
1999 | |||
2000 | |||
2001 | 8.961 | 2.486 | |
2002 | 14.426 | 3.696 | |
2003 | 15.02 | 3.712 | |
2004 | 17.013 | 3.914 | |
2005 | 17.93 | 3.691 | |
2006 | 20.283 | 4.13 | |
2007 | 20.217 | 3.885 | |
2008 | 19.372 | 3.578 | |
2009 | 17.635 | 3.108 | |
2010 | 18.629 | 3.086 | |
2011 | 37.4 | 18.437 | 3.939 |
2012 | 41.4 | 18.857 | 4.139 |
2013 | 43.9 | 15.038 | 5.106 |
2014 | 38 | 14.632 | 3.954 |
2015 | 34.4 | 11.699 | 3.763 |
2016 | 33.2 | 15.21 | 3.962 |
2017 | 35.4 | 14.007 | 4.044 |
2018 | 36.5 | 13.3 | 4.458 |
2019 | 29 | 9.283 | 3.705 |
2020 | 26 | 9.074 | 4.12 |
2021 | 25.8 |
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