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Single-cell analysis reveals islet autoantigen's immune activation in type 1 diabetes patients
In this study, we used single-cell sequencing, which can comprehensively detect the type and number of transcripts per cell, to efficiently stimulate peripheral blood mononuclear cells of type 1 diabetic patients with overlapping peptides of GAD, IA-2, and insulin antigens, and performed gene expression analysis by single-cell variable-diversity-joining sequencing and T-cell receptor repertoire analysis. Twenty male patients with type 1 diabetes mellitus participating in the KAMOGAWA-DM cohort were included. Four of them were randomly selected for BD Rhapsody system after reacting peripheral blood mononuclear cells with overlapping peptides of GAD, IA-2, and insulin antigen. Peripheral blood mononuclear cells were clustered into CD8+ T cells, CD4+ T cells, granulocytes, natural killer cells, dendritic cells, monocytes, and B cells based on Seurat analysis. In the insulin group, gene expression of inflammatory cytokines was elevated in cytotoxic CD8+ T cells and Th1 and Th17 c ells, and gene expression related to exhaustion was elevated in regulatory T cells. In T cell receptors of various T cells, the T cell receptor β chain was monoclonally increased in the TRBV28/TRBJ2-7 pairs. This study provides insights into the pathogenesis of type 1 diabetes and provides potential targets for the treatment of type 1 diabetes. © 2025 The Society for Free Radical Research Japan. All rights reserved.
Authors : Okamura T.; Kitagawa N.; Kitagawa N.; Sakai K.; Sumi M.; Kobayashi G.; Imai D.; Matsui T.; Hamaguchi M.; Fukui M.
Source : The Society for Free Radical Research Japan
Article Information
| Year | 2025 |
| Type | Article |
| DOI | 10.3164/jcbn.24-86 |
| ISSN | 09120009 |
| Volume | 76 |
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