文献类型： 外文期刊
作者： Yang, Shuo 1 ; Tian, Meijie 3 ; Dai, Yulong 4 ; Wang, Rong 2 ; Yamada, Shigehiro 1 ; Feng, Shengyong 4 ; Wang, Yunyun 7 ; Chhangani, Deepak 8 ; Ou, Tiffany 1 ; Li, Wenle 12 ; Guo, Xuan 14 ; McAdow, Jennifer 1 ; Rincon-Limas, Diego E. 8 ; Yin, Xin 6 ; Tai, Wanbo 5 ; Cheng, Gong 4 ; Johnson, Aaron 1 ;
作者机构： 1.Washington Univ, Sch Med St Louis, Dept Dev Biol, St Louis, MO 63110 USA
2.Fudan Univ, Sch Life Sci, Dept Genet & Genet Engn, Shanghai 200438, Peoples R China
3.NIH, Oncogen Sect, Genet Branch, NCI, Bethesda, MD 20892 USA
4.Tsinghua Univ, Tsinghua Univ Peking Univ Joint Ctr Life Sci, Sch Basic Med Sci, New Cornerstone Sci Lab, Beijing 100084, Peoples R China
5.Shenzhen Bay Lab, Inst Infect Dis, Shenzhen 518000, Peoples R China
6.Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Anim Dis Control & Prevent, Harbin 150069, Peoples R China
7.Huazhong Univ Sci & Technol, Dept Forens Med, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China
8.Univ Florida, Coll Med, Dept Neurol, Gainesville, FL 32611 USA
9.Univ Florida, McKnight Brain Inst, Coll Med, Dept Neurosci, Gainesville, FL 32611 USA
10.Univ Florida, Coll Med, Genet Inst, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32611 USA
11.Univ Florida, Coll Med, Norman Fixel Inst Neurol Dis, Gainesville, FL 32611 USA
12.Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China
13.Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361102, Peoples R China
14.Jinzhou Med Univ, Life Sci Inst, Jinzhou 121001, Peoples R China
15.Shenzhen Ctr Dis Control & Prevent, Inst Pathogen Organisms, Shenzhen 518055, Peoples R China
16.Southwest United Grad Sch, Kunming 650092, Peoples R China
期刊名称：SCIENCE IMMUNOLOGY （ 影响因子：17.6； 五年影响因子：19.1 ）
ISSN： 2470-9468
年卷期： 2024 年 9 卷 97 期
页码：
收录情况： SCI
摘要： Infections and neurodegenerative diseases induce neuroinflammation, but affected individuals often show nonneural symptoms including muscle pain and muscle fatigue. The molecular pathways by which neuroinflammation causes pathologies outside the central nervous system (CNS) are poorly understood. We developed multiple models to investigate the impact of CNS stressors on motor function and found that Escherichia coli infections and SARS-CoV-2 protein expression caused reactive oxygen species (ROS) to accumulate in the brain. ROS induced expression of the cytokine Unpaired 3 (Upd3) in Drosophila and its ortholog, IL-6, in mice. CNS-derived Upd3/IL-6 activated the JAK-STAT pathway in skeletal muscle, which caused muscle mitochondrial dysfunction and impaired motor function. We observed similar phenotypes after expressing toxic amyloid-beta (A beta 42) in the CNS. Infection and chronic disease therefore activate a systemic brain-muscle signaling axis in which CNS-derived cytokines bypass the connectome and directly regulate muscle physiology, highlighting IL-6 as a therapeutic target to treat disease-associated muscle dysfunction.
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