Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease.
Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease.
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DOI：
10.1016/j.immuni.2011.11.018
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发表时间：
2012-01-27
期刊：
影响因子：
32.4
通讯作者：
Stetson DB
中科院分区：
文献类型：
--
作者：
Gall A;Treuting P;Elkon KB;Loo YM;Gale M Jr;Barber GN;Stetson DB
通过检测核酸引发的I型干扰素（IFN）对抗病毒防御很重要，但也与特定的自身免疫性疾病有关。在这里，我们证明TREX1是依赖sting的抗病毒反应的基本负调节剂。介绍了组织损害。 TREX1缺陷小鼠自身免疫性疾病的逐步进展，对AGS和相关疾病的治疗产生了影响。
The type I interferon (IFN) response initiated by detection of nucleic acids is important for antiviral defense, but is also associated with specific autoimmune diseases. Mutations in the human 3′ repair exonuclease 1 (Trex1) gene cause Aicardi-Goutières syndrome (AGS), an IFN-associated autoimmune disease. However, the source of the type I IFN response and the precise mechanisms of disease in AGS remain unknown. Here, we demonstrate that Trex1 is an essential negative regulator of the STING-dependent antiviral response. We used an in vivo reporter of IFN activity in Trex1-deficient mice to localize the initiation of disease to non-hematopoietic cells. These IFNs drove T cell-mediated inflammation and an autoantibody response that targeted abundant, tissue-restricted autoantigens. However, B cells contributed to mortality independently of T cell-mediated tissue damage. These findings reveal a stepwise progression of autoimmune disease in Trex1-deficient mice, with implications for the treatment of AGS and related disorders.
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影响因子：
64.5
作者：
Stetson DB;Ko JS;Heidmann T;Medzhitov R
通讯作者：
Medzhitov R
影响因子：
9.8
作者：
Rice, Gillian;Newman, William G.;Crow, Yanick J.
通讯作者：
Crow, Yanick J.
影响因子：
30.5
作者：
通讯作者：
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DOI：
10.1084/jem.20050821
发表时间：
2005-09-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kolumam GA;Thomas S;Thompson LJ;Sprent J;Murali-Krishna K
通讯作者：
Murali-Krishna K
DOI：
10.1038/nri2587
发表时间：
2009-08
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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