缺血性肾损伤后肾脏炎症和纤维化中的 ST2+ T 调节细胞

IF 10.3 1区 医学 Q1 UROLOGY & NEPHROLOGY Journal of The American Society of Nephrology Pub Date : 2024-08-26 DOI:10.1681/ASN.0000000000000471
Vikram Sabapathy, Airi Price, Nardos Tesfaye Cheru, Rajkumar Venkatadri, Murat Dogan, Gabrielle Costlow, Saleh Mohammad, Rahul Sharma
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引用次数: 0

摘要

背景:炎症是肾脏损伤的主要原因。白细胞介素(IL)-1 家族细胞因子 IL-33 从受损细胞中释放,并通过其在许多细胞类型(包括调节性 T 细胞(Tregs))上表达的受体 ST2 调节免疫反应。虽然有人提出 IL-33 有促炎作用,但外源性 IL-33 能扩大 Tregs 并抑制肾脏炎症。然而,内源性 IL-33/ST2 对 Tregs 在解决肾损伤中的作用的贡献尚未得到研究:方法:我们利用小鼠肾缺血再灌注损伤和肾脏器官组织,通过靶向性缺失来明确 ST2 和氨肽素 (AREG) 在 Treg 细胞中的作用。研究人员分别对来自脾脏的流式分选 Tregs 和来自缺血后肾脏的 CD4 T 细胞进行了大量和单细胞 RNA 测序。在缺氧条件下,使用一种新的共培养系统分析了ST2-足量Tregs的保护作用:结果:脾脏的大量RNA测序和肾脏T细胞的单细胞RNA测序显示,ST2+ Tregs富含与Treg增殖和功能相关的基因。ST2+ Tregs中还富含AREG等修复因子的基因。在单侧缺血再灌注损伤模型中,Treg特异性缺失ST2或AREG会加重肾脏损伤和纤维化。在共培养研究中,WT 而非 ST2 缺失的 Tregs 可维持缺氧诱导的肾脏-器官活力损失,而补充 AREG 则可恢复肾脏-器官活力:我们的研究发现了Tregs中的IL-33/ST2通路在解决肾损伤中的作用。ST2+Tregs的转录组富含包括AREG在内的修复因子。Tregs中缺少ST2或AREG会加重肾损伤。Tregs以ST2和AREG依赖的方式保护肾脏器官组织免于缺氧。因此,基于 Treg 的方法可能有益于解决肾损伤问题。
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ST2 + T-Regulatory Cells in Renal Inflammation and Fibrosis after Ischemic Kidney Injury.
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来源期刊
Journal of The American Society of Nephrology
Journal of The American Society of Nephrology 医学-泌尿学与肾脏学
CiteScore
22.40
自引率
2.90%
发文量
492
审稿时长
3-8 weeks
期刊介绍: The Journal of the American Society of Nephrology (JASN) stands as the preeminent kidney journal globally, offering an exceptional synthesis of cutting-edge basic research, clinical epidemiology, meta-analysis, and relevant editorial content. Representing a comprehensive resource, JASN encompasses clinical research, editorials distilling key findings, perspectives, and timely reviews. Editorials are skillfully crafted to elucidate the essential insights of the parent article, while JASN actively encourages the submission of Letters to the Editor discussing recently published articles. The reviews featured in JASN are consistently erudite and comprehensive, providing thorough coverage of respective fields. Since its inception in July 1990, JASN has been a monthly publication. JASN publishes original research reports and editorial content across a spectrum of basic and clinical science relevant to the broad discipline of nephrology. Topics covered include renal cell biology, developmental biology of the kidney, genetics of kidney disease, cell and transport physiology, hemodynamics and vascular regulation, mechanisms of blood pressure regulation, renal immunology, kidney pathology, pathophysiology of kidney diseases, nephrolithiasis, clinical nephrology (including dialysis and transplantation), and hypertension. Furthermore, articles addressing healthcare policy and care delivery issues relevant to nephrology are warmly welcomed.
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