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Landscape of infiltrating immune cells and related genes in diabetic kidney disease

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Abstract

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.

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Acknowledgements

The authors would like to thank the Woroniecka et al for providing transcriptional data and Panovue Biotechnology inc. (Beijing, China) for providing technical guidance of multiplex immunofluorescence staining.

Funding

This study was supported by the Natural Science Foundation of Jiangxi Province (no. 20224BAB216009), Youth Talent Training Program of First Affiliated Hospital of Nanchang University (no.YFYPY202113), and the Science and Technology Plan of Jiangxi Health Planning Committee (no. 202210484).

Author information

Author notes

  1. Jiao Wang, Wen Chen and Shen Chen these authors have contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng St., Nanchang, Nanchang, 330006, Jiangxi, People’s Republic of China

    Jiao Wang, Wen Chen, Shen Chen, Ying Hu & Jixiong Xu

  2. Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, 330006, People’s Republic of China

    Jiao Wang, Wen Chen, Ying Hu & Jixiong Xu

  3. Jiangxi branch of national clinical research center for metabolic disease, Nanchang, 330006, People’s Republic of China

    Jiao Wang, Wen Chen, Ying Hu & Jixiong Xu

  4. Department of Medical Genetics and Cell biology, Medical College of Nanchang University, Nanchang, 330006, People’s Republic of China

    Guanru Yue

  5. Queen Mary School, Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China

    Shen Chen

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  1. Jiao Wang
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Contributions

JW,WC and YH collected and analyzed the data; JW, SC,and GY analyzed and interpreted the data; JX conceived the study. All authors reviewed and edited the manuscript.

Corresponding author

Correspondence to Jixiong Xu.

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There are no conflicts of interest to report.

Ethical approval

Study protocols for obtaining the paraffin-embedded specimens were approved by the First Affiliated Hospital of Nanchang University’s committee, and the samples were obtained after written informed consent.

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Wang, J., Chen, W., Chen, S. et al. Landscape of infiltrating immune cells and related genes in diabetic kidney disease. Clin Exp Nephrol 28, 181–191 (2024). https://doi.org/10.1007/s10157-023-02422-1

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  • DOI: https://doi.org/10.1007/s10157-023-02422-1

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