Interleukin-15 in kidney disease and therapeutics.

IF 2.2 3区医学 Q3 PERIPHERAL VASCULAR DISEASE

Current Opinion in Nephrology and Hypertension Pub Date : 2024-03-01 Epub Date: 2023-12-26 DOI:10.1097/MNH.0000000000000964

Gentzon Hall

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引用次数: 0

Abstract

Purpose of review: Interleukin 15 (IL-15) is a member of the IL-2 family of common gamma chain receptor cytokines with well described anti-inflammatory, pro-survival and pro-proliferative signaling properties. The cytoprotective role of IL-15 in the kidney is now coming into focus with recent reports of its beneficial actions in various forms of kidney disease. This review will summarize what is currently known about IL-15 signaling in the kidney and highlight recent evidence of its beneficial effects on kidney physiology.

Recent findings: IL-15 and its heterotrimeric receptor are expressed throughout the kidney. Like all IL-2 family cytokines, IL-15 can activate signaling through the Janus Kinase (JAK)/Signal transducer of activated T-cells (STAT), phosphoinositol-3 kinase (PI-3K)/AKT and mitogen activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways and recent evidence suggests that STAT5B is an essential transcriptional mediator of prosurvival signaling in glomerular visceral epithelial cells (i.e. podocytes). IL-15 has also been shown to suppress pro-apoptotic signaling in models of acute kidney injury and pro-fibrotic signaling in models of chronic kidney disease.

Summary: The cytoprotective properties of IL-15 suggest that it may have potential as a nonimmunosuppresive therapeutic for kidney disease. A novel class of IL-15 immunotherapies has emerged for the treatment cancer and some have demonstrated efficacy in clinical trials. These well tolerated IL-15 agonists could possibly be repurposed for the treatment of kidney disease and warrant further exploration.

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肾脏疾病和治疗中的白细胞介素-15。

综述的目的：白细胞介素 15（IL-15）是 IL-2 家族中常见的γ链受体细胞因子的成员，具有抗炎、促生存和促增殖信号转导特性。最近有报道称，IL-15 对各种形式的肾脏疾病都有益处，因此它在肾脏中的细胞保护作用正成为人们关注的焦点。本综述将总结目前已知的 IL-15 在肾脏中的信号转导，并重点介绍其对肾脏生理产生有益影响的最新证据：IL-15 及其异源受体在整个肾脏中都有表达。与所有 IL-2 家族细胞因子一样，IL-15 可通过 Janus 激酶（JAK）/活化 T 细胞信号转换器（STAT）、磷脂肌醇-3 激酶（PI-3K）/AKT 和丝裂原活化蛋白激酶激酶（MEK）/细胞外信号调节激酶（ERK）途径激活信号传导，最近的证据表明，STAT5B 是肾小球内脏上皮细胞（即荚膜细胞）中促生存信号传导的重要转录介质。即荚膜细胞）的重要转录介质。IL-15 还能抑制急性肾损伤模型中的促凋亡信号传导和慢性肾病模型中的促纤维化信号传导。目前出现了一类新型的IL-15免疫疗法来治疗癌症，其中一些已在临床试验中显示出疗效。这些耐受性良好的 IL-15 激动剂有可能被重新用于治疗肾脏疾病，值得进一步探索。

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

Current Opinion in Nephrology and Hypertension 医学-泌尿学与肾脏学

CiteScore

5.70

自引率

6.20%

发文量

132

审稿时长

6-12 weeks

期刊介绍： A reader-friendly resource, Current Opinion in Nephrology and Hypertension provides an up-to-date account of the most important advances in the field of nephrology and hypertension. Each issue contains either two or three sections delivering a diverse and comprehensive coverage of all the key issues, including pathophysiology of hypertension, circulation and hemodynamics, and clinical nephrology. Current Opinion in Nephrology and Hypertension is an indispensable journal for the busy clinician, researcher or student.