دورية أكاديمية
A neuron-immune circuit regulates neurodegeneration in the hindbrain and spinal cord of Arf1-ablated mice.
العنوان: | A neuron-immune circuit regulates neurodegeneration in the hindbrain and spinal cord of Arf1-ablated mice. |
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المؤلفون: | Wang G; The Basic Research Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA., Jin S; Department of Cell and Developmental Biology at the School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital, Fudan University, Shanghai200438, China., Liu J; Department of Cell and Developmental Biology at the School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital, Fudan University, Shanghai200438, China., Li X; Department of Cell and Developmental Biology at the School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital, Fudan University, Shanghai200438, China., Dai P; Department of Cell and Developmental Biology at the School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital, Fudan University, Shanghai200438, China., Wang Y; Department of Cell and Developmental Biology at the School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital, Fudan University, Shanghai200438, China., Hou SX; Department of Cell and Developmental Biology at the School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital, Fudan University, Shanghai200438, China.; The Basic Research Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA. |
المصدر: | National science review [Natl Sci Rev] 2023 Aug 18; Vol. 10 (12), pp. nwad222. Date of Electronic Publication: 2023 Aug 18 (Print Publication: 2023). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: China Science Publishing Country of Publication: China NLM ID: 101633095 Publication Model: eCollection Cited Medium: Internet ISSN: 2053-714X (Electronic) Linking ISSN: 2053714X NLM ISO Abbreviation: Natl Sci Rev Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: Beijing : Oxford : China Science Publishing ; Oxford University Press, [2014]- |
مستخلص: | Neuroimmune connections have been revealed to play a central role in neurodegenerative diseases (NDs). However, the mechanisms that link the central nervous system (CNS) and peripheral immune cells are still mostly unknown. We recently found that specific ablation of the Arf1 gene in hindbrain and spinal cord neurons promoted NDs through activating the NLRP3 inflammasome in microglia via peroxided lipids and adenosine triphosphate (ATP) releasing. Here, we demonstrate that IL-1β with elevated chemokines in the neuronal Arf1-ablated mouse hindbrain and spinal cord recruited and activated γδ T cells in meninges. The activated γδ T cells then secreted IFN-γ that entered into parenchyma to activate the microglia-A1 astrocyte-C3-neuronal C3aR neurotoxic pathway. Remarkably, the neurodegenerative phenotypes of the neuronal Arf1 -ablated mice were strongly ameliorated by IFN- γ or C3 knockout. Finally, we show that the Arf1-reduction-induced neuroimmune- IFN- γ-gliosis pathway exists in human NDs, particularly in amyotrophic lateral sclerosis and multiple sclerosis. Together, our results uncover a previously unknown mechanism that links the CNS and peripheral immune cells to promote neurodegeneration. (© The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.) |
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فهرسة مساهمة: | Keywords: C3; IFN-γ; disease-associated microglia; neurodegenerative diseases; reactive astrocyte; γδ T cells |
تواريخ الأحداث: | Date Created: 20240119 Latest Revision: 20240121 |
رمز التحديث: | 20240121 |
مُعرف محوري في PubMed: | PMC10794899 |
DOI: | 10.1093/nsr/nwad222 |
PMID: | 38239560 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2053-714X |
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DOI: | 10.1093/nsr/nwad222 |