Activated STING in the thymic epithelium alters T cell development and selection leading to autoimmunity
文献类型：期刊论文
| 作者 | Deng, Zimu2,3; Law, Christopher S.2; Kurra, Santosh2; Simchoni, Noa2; Shum, Anthony K.1,2 |
| 刊名 | JOURNAL OF CLINICAL INVESTIGATION
 |
| 出版日期 | 2025-09-02 |
| 卷号 | 135期号:17页码:14 |
| ISSN号 | 0021-9738 |
| DOI | 10.1172/JCI180252 |
| 通讯作者 | Deng, Zimu(dengzimu@simm.ac.cn) ; Shum, Anthony K.(anthony.shum@ucsf.edu) |
| 英文摘要 | Coatomer protein complex subunit alpha (COPA) syndrome is a monogenic disorder of immune dysregulation that leads to interstitial lung disease and high-titer autoantibodies. Constitutive activation of the innate immune molecule stimulator of interferon genes (STING) is centrally involved in disease. However, the mechanisms by which STING results in autoimmunity are not well understood in COPA syndrome and other STING-associated diseases. Prior studies showed a cell autonomous role for STING in thymocyte development. Single-cell data of human thymus demonstrated that STING is highly expressed in medullary thymic epithelial cells (mTECs) and at levels much greater than in T cells. Here, we show that in certain contexts, activated STING exerts a functional role in the thymic epithelium to alter thymocyte selection and predisposes to autoimmunity. In CopaE241K/+ mice, activated STING in mTECs amplified IFN signaling, impaired macroautophagy, and caused a defect in negative selection of T cell precursors. WT mice given a systemic STING agonist phenocopied the selection defect and showed enhanced thymic escape of a T cell clone targeting a self-antigen also expressed in melanoma. Our work demonstrates that STING activation in TECs shapes the T cell repertoire and contributes to autoimmunity, findings that are important for conditions that activate thymic STING. |
| WOS关键词 | AUTOPHAGY |
| 资助项目 | UCSF Program for Breakthrough Biomedical Research - Sandler Foundation ; Strategic Advisory Committee ; Executive Vice Chancellor and Provost Office Research Resource Program Institutional Matching Instrumentation Award ; National Natural Science Foundation of China[32170904] ; National Key R&D Program of China[2022YFA1103900] ; National Key R&D Program of China[2023YFA1800200] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences ; Sanofi-Award Fund for outstanding young talents of Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences ; NIH[R01AI168299] ; NIH[R01AI137249] |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001614776000025 |
| 出版者 | AMER SOC CLINICAL INVESTIGATION INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321971]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Deng, Zimu; Shum, Anthony K. |
| 作者单位 | 1.UCSF, Cardiovasc Res Inst, San Francisco, CA USA 2.UCSF, Dept Med Cardiovasc Res Inst, San Francisco, CA USA 3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Guangdong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Deng, Zimu,Law, Christopher S.,Kurra, Santosh,et al. Activated STING in the thymic epithelium alters T cell development and selection leading to autoimmunity[J]. JOURNAL OF CLINICAL INVESTIGATION,2025,135(17):14. |
| APA | Deng, Zimu,Law, Christopher S.,Kurra, Santosh,Simchoni, Noa,&Shum, Anthony K..(2025).Activated STING in the thymic epithelium alters T cell development and selection leading to autoimmunity.JOURNAL OF CLINICAL INVESTIGATION,135(17),14. |
| MLA | Deng, Zimu,et al."Activated STING in the thymic epithelium alters T cell development and selection leading to autoimmunity".JOURNAL OF CLINICAL INVESTIGATION 135.17(2025):14. |
入库方式： OAI收割
来源：上海药物研究所
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