Podocytes are differentiated epithelial cells which play an essential role to ensure a normal function of the glomerular filtration barrier (GFB). In addition to their adhesive properties in maintaining the integrity of the filtration barrier, they have other functions, such as synthesis of components of the glomerular basement membrane (GBM), production of vascular endothelial growth factor (VEGF), release of inflammatory proteins, and expression of complement components. They also participate in the glomerular crosstalk through multiple signalling pathways, including endothelin-1, VEGF, transforming growth factor β (TGFβ), bone morphogenetic protein 7 (BMP-7), latent transforming growth factor β-binding protein 1 (LTBP1), and extracellular vesicles. Growing literature suggests that podocytes share many properties of innate and adaptive immunity, supporting a multifunctional role ensuring a healthy glomerulus. As consequence, the “immune podocyte” dysfunction is thought to be involved in the pathogenesis of several glomerular diseases, referred to as “podocytopathies.” Multiple factors like mechanical, oxidative, and/or immunologic stressors can induce cell injury. The complement system, as part of both innate and adaptive immunity, can also define podocyte damage by several mechanisms, such as reactive oxygen species (ROS) generation, cytokine production, and endoplasmic reticulum stress, ultimately affecting the integrity of the cytoskeleton, with subsequent podocyte detachment from the GBM and onset of proteinuria. Interestingly, podocytes are found to be both source and target of complement-mediated injury. Podocytes express complement proteins which contribute to local complement activation. At the same time, they rely on several protective mechanisms to escape this damage. Podocytes express complement factor H (CFH), one of the main regulators of the complement cascade, as well as membrane-bound complement regulators like CD46 or membrane cofactor protein (MCP), CD55 or decay-accelerating factor (DAF), and CD59 or defensin. Further mechanisms, like autophagy or actin-based endocytosis, are also involved to ensure podocyte homeostasis and protection against injury. This review will provide an overview of the immune functions of podocytes and their response to immune-mediated injury, focusing on the pathogenic link between complement and podocyte damage.

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足细胞免疫功能的新见解：补体的作用

足细胞是分化的上皮细胞，对确保肾小球滤过屏障 (GFB) 的正常功能起着至关重要的作用。除了它们在维持过滤屏障完整性方面的粘附特性外，它们还具有其他功能，例如肾小球基底膜 (GBM) 成分的合成、血管内皮生长因子 (VEGF) 的产生、炎症蛋白的释放，以及补体成分的表达。它们还通过多种信号通路参与肾小球串扰，包括内皮素-1、VEGF、转化生长因子 β (TGFβ)、骨形态发生蛋白 7 (BMP-7)、潜伏转化生长因子 β 结合蛋白 1 (LTBP1)、和细胞外囊泡。越来越多的文献表明，足细胞具有许多先天免疫和适应性免疫的特性，支持确保肾小球健康的多功能作用。因此，“免疫足细胞”功能障碍被认为与几种肾小球疾病（称为“足细胞病”）的发病机制有关。机械、氧化和/或免疫应激源等多种因素可诱发细胞损伤。补体系统作为先天免疫和适应性免疫的一部​​分，还可以通过多种机制定义足细胞损伤，例如活性氧 (ROS) 生成、细胞因子生成和内质网应激，最终影响细胞骨架的完整性，随后GBM 的足细胞脱离和蛋白尿的发生。有趣的是，发现足细胞既是补体介导损伤的来源又是靶点。足细胞表达有助于局部补体激活的补体蛋白。同时，它们依靠多种保护机制来逃避这种损害。足细胞表达补体因子 H (CFH)，补体级联的主要调节剂之一，以及膜结合补体调节剂，如 CD46 或膜辅因子蛋白 (MCP)、CD55 或衰变加速因子 (DAF)，以及 CD59 或防御素。还涉及其他机制，如自噬或基于肌动蛋白的内吞作用，以确保足细胞稳态和保护免受损伤。本综述将概述足细胞的免疫功能及其对免疫介导损伤的反应，重点关注补体与足细胞损伤之间的致病联系。足细胞表达补体因子 H (CFH)，补体级联的主要调节剂之一，以及膜结合补体调节剂，如 CD46 或膜辅因子蛋白 (MCP)、CD55 或衰变加速因子 (DAF)，以及 CD59 或防御素。还涉及其他机制，如自噬或基于肌动蛋白的内吞作用，以确保足细胞稳态和保护免受损伤。本综述将概述足细胞的免疫功能及其对免疫介导损伤的反应，重点关注补体与足细胞损伤之间的致病联系。足细胞表达补体因子 H (CFH)，补体级联的主要调节剂之一，以及膜结合补体调节剂，如 CD46 或膜辅因子蛋白 (MCP)、CD55 或衰变加速因子 (DAF)，以及 CD59 或防御素。还涉及其他机制，如自噬或基于肌动蛋白的内吞作用，以确保足细胞稳态和保护免受损伤。本综述将概述足细胞的免疫功能及其对免疫介导损伤的反应，重点关注补体与足细胞损伤之间的致病联系。像自噬或基于肌动蛋白的内吞作用，也参与确保足细胞稳态和防止受伤。本综述将概述足细胞的免疫功能及其对免疫介导损伤的反应，重点关注补体与足细胞损伤之间的致病联系。像自噬或基于肌动蛋白的内吞作用，也参与确保足细胞稳态和防止受伤。本综述将概述足细胞的免疫功能及其对免疫介导损伤的反应，重点关注补体与足细胞损伤之间的致病联系。