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Regulatory T cells protect against brain damage by alleviating inflammatory response in neuromyelitis optica spectrum disorder

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单位: [1]Department of Neurology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,People’sRepublic of China [2]Department of Neurology, Mayo Clinic, Rochester, MN55905, USA
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关键词: Neuromyelitis optica spectrum disorder Regulatory T cells Inflammatory response Microglia Macrophage

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Background and purpose Neuromyelitis optica spectrum disorder (NMOSD) is mainly an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. Systemic and local inflammatory responses play a key role in the pathophysiology of NMOSD. However, the role of the crucial immunomodulators CD4(+)CD25(+) forkhead box P3(+) (Foxp3) regulatory T cells (Tregs) has not been investigated in NMOSD. Methods Twenty-five patients with anti-AQP4-postive NMOSD undergoing an attack and 21 healthy controls (HCs) were enrolled. Frequencies of T cell subsets and Tregs in the peripheral blood were assessed by flow cytometry. Additionally, a model of NMOSD using purified immunoglobulin G from anti-AQP4-antibodies-positive patients with NMOSD and human complement injected into brain of female adult C57BL/6J mice was established. Infiltrated Tregs into NMOSD mouse brain lesions were analyzed by flow cytometry, histological sections, and real-time quantitative Polymerase Chain Reaction. Astrocyte loss, demyelination, and inflammatory response were also evaluated in our NMOSD mouse model. Finally, we examined the effects of both depletion and adoptive transfer of Tregs. Results The percentage of Tregs, especially naive Tregs, among total T cells in peripheral blood was significantly decreased in NMOSD patients at acute stage when compared to HCs. Within our animal model, the number and proportion of Tregs among CD4(+) T cells were increased in the lesion of mice with NMOSD. Depletion of Tregs profoundly enhanced astrocyte loss and demyelination in these mice, while adoptive transfer of Tregs attenuated brain damage. Mechanistically, the absence of Tregs induced more macrophage infiltration, microglial activation, and T cells invasion, and modulated macrophages/microglia toward a classical activation phenotype, releasing more chemokines and pro-inflammatory cytokines. In contrast, Tregs transfer ameliorated immune cell infiltration in NMOSD mice, including macrophages, neutrophils, and T cells, and skewed macrophages and microglia towards an alternative activation phenotype, thereby decreasing the level of chemokines and pro-inflammatory cytokines. Conclusion Tregs may be key immunomodulators ameliorating brain damage via dampening inflammatory response after NMOSD.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 2 区 免疫学 2 区 神经科学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 免疫学 1 区 神经科学
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出版当年[2019]版:
Q1 IMMUNOLOGY Q1 NEUROSCIENCES
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Q1 IMMUNOLOGY Q1 NEUROSCIENCES

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第一作者单位: [1]Department of Neurology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,People’sRepublic of China
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