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通过 CyTOF 技术研究长期 1 型糖尿病患者的免疫特征。

Investigating immune profile by CyTOF in individuals with long-standing type 1 diabetes.

机构信息

Department of ENT, Head and Neck Surgery, NU Hospital Group, Trollhättan, Sweden.

Department of Otorhinolaryngology, Head and Neck Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.

出版信息

Sci Rep. 2023 May 20;13(1):8171. doi: 10.1038/s41598-023-35300-7.

DOI:10.1038/s41598-023-35300-7
PMID:37210405
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10199897/
Abstract

Type 1 diabetes (T1D) is an autoimmune disease caused by T-cell mediated destruction of pancreatic beta cells. Eosinophils are found in pancreatic tissue from individuals with T1D. Eosinophilic suppression of T cells is dependent of the protein galectin-10. Little is known when it comes to the role of eosinophil granulocytes in type 1 diabetes. Here we show that individuals with long-standing T1D had lower levels of galectin-10 eosinophils and a subgroup of galectin-10 eosinophils were entirely absent in all T1D patients. In addition, 7% immature eosinophils were present in the circulation of T1D patients whereas 0.8% in healthy individuals. Furthermore, higher levels of CD4+CD8+ T cells and Th17 cells were observed in patients with T1D. Blood samples from 12 adult individuals with long-standing T1D and 12 healthy individuals were compared using cytometry by time-of-flight. Lower levels of galectin-10 eosinophils, which are potent T cell suppressors, in individuals with T1D could indicate that activated T cells are enabled to unrestrictedly kill the insulin producing beta cells. This is the first study showing absence of galectin-10 eosinophilic subgroup in individuals with T1D compared with healthy controls. This study is a first important step toward unraveling the role of the eosinophils in patients with T1D.

摘要

1 型糖尿病(T1D)是一种由 T 细胞介导的胰腺β细胞破坏引起的自身免疫性疾病。嗜酸性粒细胞存在于 T1D 患者的胰腺组织中。嗜酸性粒细胞对 T 细胞的抑制作用依赖于蛋白半乳糖凝集素-10。目前对于嗜酸性粒细胞在 1 型糖尿病中的作用知之甚少。在这里,我们发现患有长期 T1D 的个体中半乳糖凝集素-10 嗜酸性粒细胞水平较低,并且所有 T1D 患者的半乳糖凝集素-10 嗜酸性粒细胞亚群完全缺失。此外,T1D 患者的循环中存在 7%的未成熟嗜酸性粒细胞,而健康个体中为 0.8%。此外,T1D 患者中观察到 CD4+CD8+T 细胞和 Th17 细胞水平升高。使用飞行时间流式细胞术比较了 12 名患有长期 T1D 的成年个体和 12 名健康个体的血液样本。T1D 个体中半乳糖凝集素-10 嗜酸性粒细胞水平较低,而半乳糖凝集素-10 嗜酸性粒细胞是强有力的 T 细胞抑制剂,这表明活化的 T 细胞能够不受限制地杀死产生胰岛素的β细胞。这是第一项研究,与健康对照组相比,T1D 个体中存在半乳糖凝集素-10 嗜酸性粒细胞亚群缺失。这项研究是揭示嗜酸性粒细胞在 T1D 患者中作用的重要第一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fdd/10199897/d0ba44783c38/41598_2023_35300_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fdd/10199897/35afc06f8349/41598_2023_35300_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fdd/10199897/92602ad9a012/41598_2023_35300_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fdd/10199897/6bb7800b979e/41598_2023_35300_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fdd/10199897/d0ba44783c38/41598_2023_35300_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fdd/10199897/35afc06f8349/41598_2023_35300_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fdd/10199897/fdd9fff100c3/41598_2023_35300_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fdd/10199897/3589f6c6709f/41598_2023_35300_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fdd/10199897/92602ad9a012/41598_2023_35300_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fdd/10199897/6bb7800b979e/41598_2023_35300_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fdd/10199897/d0ba44783c38/41598_2023_35300_Fig6_HTML.jpg

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本文引用的文献

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Activated but functionally impaired memory Tregs are expanded in slow progressors to type 1 diabetes.在缓慢进展为 1 型糖尿病的患者中,活化但功能受损的记忆性调节性 T 细胞(Tregs)扩增。
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Eosinophils interact with thymocytes and proliferate in the human thymus.嗜酸性粒细胞与人胸腺细胞相互作用并在人类胸腺中增殖。
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