Landscape of infiltrating immune cells and related genes in diabetic kidney disease,Clinical and Experimental Nephrology

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Landscape of infiltrating immune cells and related genes in diabetic kidney disease
Clinical and Experimental Nephrology ( IF 2.2 ) Pub Date : 2023-10-26 , DOI: 10.1007/s10157-023-02422-1
Jiao Wang _{1,

2,

3} , Wen Chen _{1,

2,

3} , Shen Chen _{1,

4} , Guanru Yue ₅ , Ying Hu _{1,

2,

3} , Jixiong Xu _{1,

2,

3}

Affiliation

Introduction

Diabetic kidney disease (DKD) is one of the prominent microvascular complications of diabetes and the leading cause of end-stage renal disease. Inflammation plays a crucial role in the development and progression of DKD. Currently, only a few studies depict the landscape of infiltrating immune cells and their potential regulatory network in DKD. To gain a better understanding of the role of immune cells in the renal microenvironment, we sought to reveal the profile of infiltrating immune cells and their potential regulatory network in DKD.

Methods

We obtained the transcriptomes and the corresponding clinical data of 19 DKD and 25 control samples from the Gene Expression Omnibus and Nephroseq databases, respectively. Thereafter, we conducted an analysis on the infiltrating immune cells and identified immune-related differentially expressed genes through bioinformatics. Finally, correlation analyses among immune cells, immune genes, and clinical manifestations were performed, and differentially infiltrating immune cell subsets were verified through multiplex immunofluorescence staining.

Results

We demonstrated the landscape of infiltrating immune cells in patients with DKD and identified the top five hub immune regulatory genes (C3, IL7R, TYROBP, BMP2, and CXCL6). Three of the core genes (C3, BMP2, and CXCL6) were significantly correlated with the estimated glomerular filtration rate. Through multiplex immunofluorescence staining, we verified that macrophage numbers were remarkably elevated, whereas Treg cells were remarkably reduced in diabetic kidney tissues. Th2 cells were scarce in the kidney tissue.

Conclusion

Collectively, our findings shed light on new, possible therapeutic strategies for DKD, from an immune microenvironment perspective.

中文翻译：

糖尿病肾病中浸润免疫细胞和相关基因的景观

介绍

糖尿病肾病（DKD）是糖尿病突出的微血管并发症之一，也是导致终末期肾病的主要原因。炎症在 DKD 的发生和进展中起着至关重要的作用。目前，只有少数研究描述了 DKD 中浸润性免疫细胞及其潜在调控网络的情况。为了更好地了解免疫细胞在肾脏微环境中的作用，我们试图揭示 DKD 中浸润免疫细胞的概况及其潜在的调节网络。

方法

我们分别从 Gene Expression Omnibus 和 Nephroseq 数据库中获得了 19 个 DKD 和 25 个对照样本的转录组和相应的临床数据。此后，我们对浸润的免疫细胞进行了分析，并通过生物信息学鉴定了免疫相关的差异表达基因。最后，进行免疫细胞、免疫基因和临床表现之间的相关性分析，并通过多重免疫荧光染色验证差异浸润的免疫细胞亚群。

结果

我们展示了 DKD 患者浸润免疫细胞的情况，并确定了前 5 个中枢免疫调节基因（ C3 、 IL7R 、 TYROBP 、 BMP2和CXCL6 ）。三个核心基因（ C3 、 BMP2和CXCL6 ）与估计的肾小球滤过率显着相关。通过多重免疫荧光染色，我们证实糖尿病肾组织中巨噬细胞数量显着升高，而Treg细胞显着减少。肾组织中 Th2 细胞稀缺。