糖尿病肾病（DN）是糖尿病的常见并发症，其主要致病因素是代谢异常和血流动力学改变。然而研究表明，免疫炎症反应在DN发病机制中也发挥着重要作用。因此，在本研究中，我们利用孟德尔随机化（MR）和生物信息学技术分析了炎症因子与DN之间的因果关系和免疫浸润。我们使用以反方差加权分析结果为主的双样本MR分析了91种炎症因子与DN之间的因果关系。在MR分析的基础上，利用免疫细胞浸润分析进一步探讨DN中炎症因子的免疫机制。 MR分析表明DN与IL1A、半胱天冬酶8(CASP8)、巨噬细胞集落刺激因子1、IL10、STAM结合蛋白和肿瘤坏死因子配体超家族成员12(TNFSF12)之间存在正因果关系，而DN与DN之间存在负因果关系。以及胱抑素 D、成纤维细胞生长因子 19、神经营养因子和 TNFSF14。 CASP8的致病机制可能涉及招募CD4 T细胞和巨噬细胞进行DN浸润。在这项研究中，我们发现 DN 与 IL1A、CASP8、巨噬细胞集落刺激因子 1、IL10、STAM 结合蛋白、TNFSF12、胱抑素 D、成纤维细胞生长因子 19、neurturin 和 TNFSF14 之间存在因果关系。生物信息免疫浸润分析进一步揭示，CASP8通过影响T细胞和巨噬细胞等免疫细胞的浸润来调节DN。版权所有©2024作者。由 Wolters Kluwer Health, Inc. 出版

The main causative factors of diabetic nephropathy (DN), a common complication of diabetes mellitus, are metabolic abnormalities and hemodynamic changes. However, studies have shown that the immune-inflammatory response also plays an important role in DN pathogenesis. Therefore, in this study, we analyzed the causal relationship and immune infiltration between inflammatory factors and DN using Mendelian randomization (MR) and bioinformatics techniques. We analyzed the causal relationship between 91 inflammatory factors and DN using two-sample MR dominated by the results of inverse variance-weighted analysis. Based on the MR analysis, the immune mechanism of inflammatory factors in DN was further explored using immune cell infiltration analysis. MR analysis indicated a positive causal relationship between DN and IL1A, caspase 8 (CASP8), macrophage colony-stimulating factor 1, IL10, STAM-binding protein, and tumor necrosis factor ligand superfamily member 12 (TNFSF12) and a negative causal relationship between DN and cystatin D, fibroblast growth factor 19, neurturin, and TNFSF14. The pathogenic mechanism of CASP8 may involve the recruitment of CD4+ T cells and macrophages for DN infiltration. In this study, we found a causal relationship between DN and IL1A, CASP8, macrophage colony-stimulating factor 1, IL10, STAM-binding protein, TNFSF12, cystatin D, fibroblast growth factor 19, neurturin, and TNFSF14. Bioinformatic immune infiltration analysis further revealed that CASP8 regulates DN by influencing the infiltration of immune cells, such as T cells and macrophages.Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.