CD8 + CD103 + iTregs protect against ischemia-reperfusion-induced acute kidney Injury by inhibiting pyroptosis

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Apoptosis Pub Date : 2024-07-28 DOI:10.1007/s10495-024-02001-z

Qiuju Chen, Xiao Zhang, Hui Yang, Guangxuan Luo, Xin Zhou, Zhenjian Xu, Anping Xu

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Abstract

The occurrence of acute kidney injury (AKI) is elevated, one of the main causes is ischemia-reperfusion (I/R). However, no specific therapy is currently available to treat I/R-induced AKI (I/R-AKI). Treg cells have been demonstrated to perform an anti-inflammatory role in a range of autoimmune and inflammatory illnesses. However, there is limited available information about the possible functions of CD8 + CD103 + iTregs in I/R-AKI. We utilized renal tubular epithelial cells (RTECs) subjected to hypoxia-reoxygenation (H/R) and I/R-AKI mouse model to investigate whether CD8 + CD103 + iTregs could attenuate AKI and the underlying mechanism. In vitro, co-cultured with CD8 + CD103 + iTregs alleviated H/R-induced cell injury. After treatment of CD8 + CD103 + iTregs rather than control cells, a significant improvement of I/R-AKI was observed in vivo, including decreased serum creatinine (sCr) and blood urea nitrogen (BUN) levels, reduced renal pathological injury, lowered tubular apoptosis and inhibition of the transition from AKI to chronic kidney disease (CKD). Mechanically, CD8 + CD103 + iTregs alleviated H/R-induced cell injury and I/R-AKI partly by suppressing RTECs pyroptosis via inhibiting the NLRP3/Caspase-1 axis. Our study provides a novel perspective on the possibility of CD8 + CD103 + iTregs for the treatment of I/R-AKI.

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CD8 + CD103 + iTregs 通过抑制热蛋白沉积防止缺血再灌注诱发的急性肾损伤

急性肾损伤（AKI）发生率升高，其中一个主要原因是缺血再灌注（I/R）。然而，目前还没有治疗缺血再灌注引起的急性肾损伤（I/R-AKI）的特效疗法。Treg 细胞已被证实在一系列自身免疫性和炎症性疾病中发挥抗炎作用。然而，有关 CD8 + CD103 + iTregs 在 I/R-AKI 中可能发挥的功能的现有信息非常有限。我们利用肾小管上皮细胞（RTECs）进行缺氧-复氧（H/R）和I/R-AKI小鼠模型，研究CD8 + CD103 + iTregs是否能减轻AKI及其内在机制。在体外，与 CD8 + CD103 + iTregs 共同培养可减轻 H/R 诱导的细胞损伤。经 CD8 + CD103 + iTregs 而非对照细胞处理后，体内观察到 I/R-AKI 明显改善，包括降低血清肌酐（sCr）和血尿素氮（BUN）水平、减少肾脏病理损伤、降低肾小管凋亡和抑制从 AKI 向慢性肾病（CKD）的转变。从机制上讲，CD8 + CD103 + iTregs能减轻H/R诱导的细胞损伤和I/R-AKI，部分原因是它们通过抑制NLRP3/Caspase-1轴抑制了RTECs的热凋亡。我们的研究为 CD8 + CD103 + iTregs 治疗 I/R-AKI 的可能性提供了一个新的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Apoptosis 生物-生化与分子生物学

CiteScore

9.10

自引率

4.20%

发文量

审稿时长

1 months

期刊介绍： Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.