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Increased ocular plasma cells induce damaging α-synuclein+ microglia in autoimmune uveitis

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资源类型：
Pubmed体系：
作者：
Li Minghao[1,2,3,4] * ; Feng Meng[5,6] * ; Liu Tingting[7,8] * ; Duan Songqi[9] * ; Man Xuejing[10] ; Yuan Xiaomeng[7] ; Wang Lijie[2] ; Sun Yu[7] ; Wei Xunbin[13,14,15,16,17] ; Fu Qiang[11,12] ; Sun Baofa[18] ; Lin Wei[1,2,3,4] ;
机构： [1]Department of Rheumatology and Autoimmunology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China [2]School of Clinical and Basic Medicine, Shandong First Medical University &Shandong Academy of Medical Sciences, Jinan, China [3]Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Medicine and Health Key Laboratory of Rheumatism, The First Affiliated Hospital of Shandong First Medical University, Jinan, China [4] Department of Critical-care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China [5] Department of Laboratory Medicine, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Deputy 2, West Road Weiyang, Qindu District, Xianyang, Shaanxi 712000, China [6]The First Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Weiyang West Road, Xianyang City 710077 Shaanxi Province, China [7]Shandong Eye Hospital, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China [8]Department of Ophthalmology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, China [9]College of Food Science, Sichuan Agricultural University, Ya an, China [10]Department of Ophthalmology, Yuhuangding Hospital, Yantai, China [11]Shanghai Jiao Tong University, Subei Research Institute, Anti-aging Innovation Center, Shanghai, China [12]School of Pharmacology, Institute of Aging Medicine, Binzhou Medical University,Yantai, China [13] Biomedical Engineering Department, Peking University, Beijing, China [14] School of Biomedical Engineering, Anhui Medical University, Hefei, China [15] Institute of Medical Technology, Peking University Health Science Center, Beijing, China [16] Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China [17] International Cancer Institute, Peking University, Beijing, China [18]State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin, China
出处：
DOI： 10.1016/j.mucimm.2025.02.007
ISSN：

关键词： Ocular immunology single-cell RNA sequencing Autoimmune uveitis Inflammatory factors Plasma cells

摘要：
Autoimmune uveitis (AIU) is an immune-inflammatory disease that can lead to blindness. However, incomplete understanding of the involved immune cell subsets and their contributions to retinal injury has hindered the development of effective AIU therapies. Using single-cell RNA sequencing and immunofluorescence, we identified α-synuclein+ microglia as the primary subset of damaged ocular cells in the eyes of the experimental autoimmune uveitis (EAU) mouse model. Ocular-infiltrating plasma cells (PCs) were shown to express multiple inflammatory factors, particularly TNF-α, which promoted the production of α-synuclein+ microglia. Studies of heterogeneous PC subtypes revealed that MUC1- PCs represent the primary pathogenic subset, secreting multiple cytokines. Although MUC1+ PCs expressed TGF-β, they exhibited long-lived characteristics and secreted IgG and IgM, thereby prolonging disease progression. Finally, the small G protein Rab1A, also expressed in the PCs of Vogt-Koyanagi-Harada (VKH) patients, was found to mediate autophagy and NF-κB expression, influencing PCs survival and inflammatory responses. Silencing or knocking down Rab1A in PCs inhibited their survival. This study elucidates potential mechanisms underlying the neuroimmune inflammatory response and highlights the previously unrecognized role of infiltrating PCs in AIU, offering novel therapeutic targets for this disease.Copyright © 2025. Published by Elsevier Inc.

基金：
This work was funded by the National Natural Science Foundation of China (32170497, 32261160571, 82471061), The Special Fund for Research on National Major Research Instruments of China (62027824), the Science and Technology Plan of Yantai City Government (2019MSGY134), and the Yantai Double Hundred Program, University and Locality Collaborative Program (2021XDHZ082). Shandong Natural Science Foundation (ZR2023MH035, ZR2023MH262), and Youth Science Foundation Cultivation Support Program (Natural Science) of Shandong First Medical University &Shandong Academy of Medical Sciences (202201-009)
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
无
最新[2023]版：
大类 | 2 区 医学
小类 | 2 区 免疫学
第一作者：
第一作者机构： [1]Department of Rheumatology and Autoimmunology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China [2]School of Clinical and Basic Medicine, Shandong First Medical University &Shandong Academy of Medical Sciences, Jinan, China [3]Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Medicine and Health Key Laboratory of Rheumatism, The First Affiliated Hospital of Shandong First Medical University, Jinan, China [4] Department of Critical-care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Rheumatology and Autoimmunology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China [2]School of Clinical and Basic Medicine, Shandong First Medical University &Shandong Academy of Medical Sciences, Jinan, China [3]Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Medicine and Health Key Laboratory of Rheumatism, The First Affiliated Hospital of Shandong First Medical University, Jinan, China [4] Department of Critical-care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China [11]Shanghai Jiao Tong University, Subei Research Institute, Anti-aging Innovation Center, Shanghai, China [12]School of Pharmacology, Institute of Aging Medicine, Binzhou Medical University,Yantai, China
推荐引用方式(GB/T 7714)：
Li Minghao,Feng Meng,Liu Tingting,et al.Increased ocular plasma cells induce damaging α-synuclein+ microglia in autoimmune uveitis[J].Mucosal Immunology.2025,doi:10.1016/j.mucimm.2025.02.007.
APA：
Li Minghao,Feng Meng,Liu Tingting,Duan Songqi,Man Xuejing...&Lin Wei.(2025).Increased ocular plasma cells induce damaging α-synuclein+ microglia in autoimmune uveitis.Mucosal Immunology,,
MLA：
Li Minghao,et al."Increased ocular plasma cells induce damaging α-synuclein+ microglia in autoimmune uveitis".Mucosal Immunology .(2025)

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