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靶向 1 型糖尿病中的自身反应性 CD8 T 细胞受体:单细胞 RNA 测序免疫治疗的见解。

Targeting the autoreactive CD8 T-cell receptor in type 1 diabetes: Insights from scRNA-seq for immunotherapy.

机构信息

Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.

Department of Respiratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.

出版信息

Pharmacol Res. 2024 Nov;209:107433. doi: 10.1016/j.phrs.2024.107433. Epub 2024 Sep 27.

Abstract

Type 1 Diabetes (T1D) is an autoimmune disease characterized by the attack and destruction of Pancreatic islet beta cells by T cells. Understanding the role of T-cell receptor (TCR) in the development of T1D is of paramount importance. This study employs single-cell RNA sequencing (scRNA-seq) to delve into the mechanistic actions and potential therapeutic applications of autoreactive stem cell-like CD8 TCR in T1D. By retrieving T-cell data from non-obese diabetic (NOD) mice via the GEO database, it was revealed that CD8 T cells are the predominant T-cell subset in the pancreatic tissue of T1D mice, along with the identification of T-cell marker genes closely associated with T1D. Moreover, the gene TRAJ23 exhibits a preference for T1D, and its knockout alleviates T1D symptoms and adverse reactions in NOD mice. Additionally, engineered TCR-T cells demonstrate significant cytotoxicity towards β cells in T1D.

摘要

1 型糖尿病(T1D)是一种自身免疫性疾病,其特征是 T 细胞攻击和破坏胰岛β细胞。了解 T 细胞受体(TCR)在 T1D 中的作用至关重要。本研究采用单细胞 RNA 测序(scRNA-seq)深入研究自身反应性干细胞样 CD8 TCR 在 T1D 中的作用机制和潜在的治疗应用。通过从 GEO 数据库中检索非肥胖型糖尿病(NOD)小鼠的 T 细胞数据,研究发现 CD8 T 细胞是 T1D 小鼠胰腺组织中的主要 T 细胞亚群,并鉴定出与 T1D 密切相关的 T 细胞标记基因。此外,基因 TRAJ23 对 T1D 具有偏好性,其敲除可减轻 NOD 小鼠的 T1D 症状和不良反应。此外,工程 TCR-T 细胞对 T1D 中的β细胞具有显著的细胞毒性。

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