The article "Understanding the Podocyte Immune Responses in Proteinuric Kidney Diseases: From Pathogenesis to Therapy" by Hong Jiang et al. provides a comprehensive review of the role of podocytes in proteinuric kidney diseases and their immune responses. Podocytes, essential for maintaining the glomerular filtration barrier, are vulnerable to damage from both intrinsic and extrinsic factors, leading to proteinuria and chronic kidney disease (CKD). The authors highlight the dual nature of podocytes, which not only contribute to the integrity of the filtration barrier but also exhibit immune cell-like characteristics, participating in both innate and adaptive immunity. The review covers several key aspects: 1. **Innate Immune Responses**: Podocytes express pattern recognition receptors (PRRs) such as Toll-like Receptors (TLRs) and Nod-like receptors (NLRs), which play crucial roles in recognizing and responding to pathogens and danger signals. TLR4 activation, for example, can contribute to podocyte damage and interstitial fibrosis. 2. **Adaptive Immune Responses**: Podocytes can express major histocompatibility complex (MHC) class I and II antigens, facilitating interactions with T cells. CD4+ and CD8+ T cells are involved in modulating immune responses, with CD4+ T cells activating innate and adaptive immune cells and CD8+ T cells exerting cytotoxic effects. 3. **Crosstalk Between Podocytes and Other Cells**: The interaction between podocytes and other glomerular cells, such as endothelial cells and mesangial cells, is critical in the development of glomerular diseases. For instance, mitochondrial oxidative stress in endothelial cells can lead to increased Endothelin-1 (Edn1) expression and subsequent podocyte damage. 4. **Common Proteinuric Glomerular Diseases**: The article discusses specific diseases like minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), primary membranous nephropathy (pMN), and lupus nephritis with podocyte injury. Each disease is associated with distinct immune mechanisms, and the authors provide insights into the pathogenesis and potential therapeutic targets. 5. **Therapeutic Strategies**: The review concludes with an overview of current standard therapies, including immunosuppressive drugs like glucocorticoids and calcineurin inhibitors, which aim to reduce proteinuria and modulate hyperactive immune responses. The authors emphasize the need for further research to identify new therapeutic targets and improve the treatment of podocyte-related kidney diseases. Overall, the article provides a detailed understanding of the complex mechanisms underlying podocyte immune responses in proteinuric kidney diseases and highlights the potential for developing novel therapeutic approaches.The article "Understanding the Podocyte Immune Responses in Proteinuric Kidney Diseases: From Pathogenesis to Therapy" by Hong Jiang et al. provides a comprehensive review of the role of podocytes in proteinuric kidney diseases and their immune responses. Podocytes, essential for maintaining the glomerular filtration barrier, are vulnerable to damage from both intrinsic and extrinsic factors, leading to proteinuria and chronic kidney disease (CKD). The authors highlight the dual nature of podocytes, which not only contribute to the integrity of the filtration barrier but also exhibit immune cell-like characteristics, participating in both innate and adaptive immunity. The review covers several key aspects: 1. **Innate Immune Responses**: Podocytes express pattern recognition receptors (PRRs) such as Toll-like Receptors (TLRs) and Nod-like receptors (NLRs), which play crucial roles in recognizing and responding to pathogens and danger signals. TLR4 activation, for example, can contribute to podocyte damage and interstitial fibrosis. 2. **Adaptive Immune Responses**: Podocytes can express major histocompatibility complex (MHC) class I and II antigens, facilitating interactions with T cells. CD4+ and CD8+ T cells are involved in modulating immune responses, with CD4+ T cells activating innate and adaptive immune cells and CD8+ T cells exerting cytotoxic effects. 3. **Crosstalk Between Podocytes and Other Cells**: The interaction between podocytes and other glomerular cells, such as endothelial cells and mesangial cells, is critical in the development of glomerular diseases. For instance, mitochondrial oxidative stress in endothelial cells can lead to increased Endothelin-1 (Edn1) expression and subsequent podocyte damage. 4. **Common Proteinuric Glomerular Diseases**: The article discusses specific diseases like minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), primary membranous nephropathy (pMN), and lupus nephritis with podocyte injury. Each disease is associated with distinct immune mechanisms, and the authors provide insights into the pathogenesis and potential therapeutic targets. 5. **Therapeutic Strategies**: The review concludes with an overview of current standard therapies, including immunosuppressive drugs like glucocorticoids and calcineurin inhibitors, which aim to reduce proteinuria and modulate hyperactive immune responses. The authors emphasize the need for further research to identify new therapeutic targets and improve the treatment of podocyte-related kidney diseases. Overall, the article provides a detailed understanding of the complex mechanisms underlying podocyte immune responses in proteinuric kidney diseases and highlights the potential for developing novel therapeutic approaches.