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肾脏病治疗的新时代:NLRP3炎性小体和细胞因子靶向疗法。

A new era in the treatment of kidney diseases: NLRP3 inflammasome and cytokine-targeted therapies.

作者信息

Leventoğlu Emre, Bakkaloğlu Sevcan A

机构信息

Department of Pediatric Nephrology, Konya City Hospital, Konya, Turkey.

Faculty of Medicine, Department of Pediatric Nephrology, Gazi University, Ankara, Turkey.

出版信息

Pediatr Nephrol. 2025 May;40(5):1515-1521. doi: 10.1007/s00467-024-06578-0. Epub 2024 Nov 1.

Abstract

The kidneys are crucial for filtering blood, managing overall body water, electrolyte, and acid-base balance, and regulating blood pressure. They remove metabolic waste products, toxins, and drugs. In addition, they limit inflammation by clearing cytokines and reduce immune cell activation by removing bacterial components. Dendritic cells (DCs) in the kidney maintain peripheral tolerance. About 85% of filtered water is reabsorbed by the proximal tubule, exposing distal nephron cells to high concentrations of low molecular weight antigens. These antigens are captured by DCs, helping to inactivate potentially autoreactive T cells and maintain tolerance to circulating antigens. In kidney failure, immune function is severely compromised due to the retention of toxins and cytokines, which activate immune cells and increase systemic inflammation. The kidneys are also vulnerable to immune-mediated diseases. Loss of immune homeostasis, characterized by over- or under-activity of the immune response, can adversely affect kidney function. With advances in immunology and cellular biology, biologic therapies targeting various pathways involved in the pathophysiology of kidney diseases are being developed. In this review, the immunologic aspects of kidney diseases and focus on cytokine-based therapies that may hold promise for the treatment of kidney diseases in the future will be presented.

摘要

肾脏对于过滤血液、维持全身水、电解质及酸碱平衡以及调节血压至关重要。它们能清除代谢废物、毒素和药物。此外,肾脏通过清除细胞因子来限制炎症,并通过去除细菌成分来减少免疫细胞的激活。肾脏中的树突状细胞(DCs)维持外周耐受。约85%被滤过的水在近端小管被重吸收,使远端肾单位细胞暴露于高浓度的低分子量抗原中。这些抗原被DCs捕获,有助于使潜在的自身反应性T细胞失活,并维持对循环抗原的耐受。在肾衰竭时,由于毒素和细胞因子的潴留,免疫功能会严重受损,这些毒素和细胞因子会激活免疫细胞并增加全身炎症。肾脏也易患免疫介导的疾病。免疫稳态的丧失,表现为免疫反应过度或不足,会对肾功能产生不利影响。随着免疫学和细胞生物学的进展,针对肾脏疾病病理生理学中各种相关途径的生物疗法正在研发中。在本综述中,将阐述肾脏疾病的免疫学方面,并重点介绍可能对未来肾脏疾病治疗具有前景的基于细胞因子的疗法。

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