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Journal of neuroinflammation
May 27, 2024;21 (1): 136.

CCR5-overexpressing mesenchymal stem cells protect against experimental autoimmune uveitis: insights from single-cell transcriptome analysis.

Fa Yuan, Rong Zhang, Jiani Li, Qiannan Lei, Shuyi Wang, Fanying Jiang, Yanan Guo, Mengqing Xiang
Author Information
  1. Fa Yuan: State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
  2. Rong Zhang: State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
  3. Jiani Li: State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
  4. Qiannan Lei: State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
  5. Shuyi Wang: State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
  6. Fanying Jiang: State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
  7. Yanan Guo: State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
  8. Mengqing Xiang: State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China. xiangmq3@mail.sysu.edu.cn.
PMID: 38802924 DOI: 10.1186/s12974-024-03134-3

Abstract

Autoimmune uveitis is a leading cause of severe vision loss, and animal models provide unique opportunities for studying its pathogenesis and therapeutic strategies. Here we employ scRNA-seq, RNA-seq and various molecular and cellular approaches to characterize mouse models of classical experimental autoimmune uveitis (EAU), revealing that EAU causes broad retinal neuron degeneration and marker downregulation, and that M��ller glia may act as antigen-presenting cells. Moreover, EAU immune response is primarily driven by Th1 cells, and results in dramatic upregulation of CC chemokines, especially CCL5, in the EAU retina. Accordingly, overexpression of CCR5, a CCL5 receptor, in mesenchymal stem cells (MSCs) enhances their homing capacity and improves their immunomodulatory outcomes in preventing EAU, by reducing infiltrating T cells and activated microglia and suppressing Nlrp3 inflammasome activation. Taken together, our data not only provide valuable insights into the molecular characteristics of EAU but also open an avenue for innovative MSC-based therapy.

Keywords

CCL5/CCR5 Experimental autoimmune uveitis Mesenchymal stem cells scRNA-seq

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Grants

  1. 81970794/National Natural Science Foundation of China
  2. 2021ZD0202603/"Technology Innovation 2030-Major Projects" on Brain Science and Brain-Like Computing of the Ministry of Science and Technology of China
  3. 2023B1212060018/The Science and Technology Planning Project of Guangdong Province

MeSH Term

Animals
Mice
Mesenchymal Stem Cells
Uveitis
Receptors, CCR5
Mice, Inbred C57BL
Single-Cell Analysis
Autoimmune Diseases
Gene Expression Profiling
Disease Models, Animal
Female
Single-Cell Gene Expression Analysis

Chemicals

Receptors, CCR5
CCR5 protein, mouse
Journal Article
Article has an altmetric score of 2

Word Cloud

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