Decoding the Intercellular Cross-Talking Between Immune Cells and Renal Innate Cells in Diabetic Kidney Disease by Bioinformatics

Abstract

Aim

Diabetic kidney disease (DKD) continues to be devastating complication of diabetes mellitus. Immune response and inflammatory reaction play essential roles in the progression of DKD. But the specific mechanism of immune cells, and their act on renal innate cells remains unclear. This article focused on immune cells and their communication with renal innate cells to provide bioinformatic evidence for further understanding the immune mechanism in DKD.

Methods

Data were analyzed to evaluate the differentially expressed genes (DEGs) and their pathways in DKD patients and mice. Gene set enrichment analysis (GSEA) was used to explore the immune inflammation-related pathways. CIBERSORT was applied to evaluate the distribution of inflammatory cells in different states. Cell-type DEGs and their enrichment pathways were further explored in podocytes, proximal tubule cells and injured tubule cells. Cellchat was used to reveal the cellular communication between immune cells and renal innate cells in DKD.

Results

GO and KEGG analysis showed that DEGs were mainly enriched in immune inflammation-related pathways. Monocytes, M2 macrophages and T cells were significantly increased in DKD samples, especially in renal tubule. ScRNA datasets showed that the immune cells number in DKD were significantly increased. Cell-type DEGs were involved in kidney growth and development. In DKD, the interaction numbers and strength between immune cells and innate cells were significantly increased. VISTANT, SPP1 and IGF signal flow were increased in DKD. SPP1-CD44, NRG1-ERBB4, NAMPT-INSR, and Igf1-Igf1r receptor ligand pairs were enhanced in DKD, which mediated the communication between immune-inflammatory cells and innate cells.

Conclusion

Our study explored the pathogenesis of renal injury promoted by immunoinflammatory in DKD. VISTANT, SPP1, and IGF signaling pathways and SPP1-CD44, NRG1-ERBB4, NAMPT-INSR, and Igf1- Igf1r receptor ligand pairs might occupy essential place in the occurrence and progress of DKD.

Keywords:

• diabetic kidney disease
• immune cells
• renal innate cells
• bioinformatics

Ethics Approval and Informed Consent

All experiments and methods were performed in accordance with relevant guidelines and regulations. This study protocol was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University. Informed consent was obtained from all individual participants included in the study. We strictly abided the principles of the Declaration of Helsinki.

Acknowledgments

We thank Dr. Jiangming Zeng (University of Macau) and all the members of his bioinformatics team for generously sharing their experience and codes. This work was supported by grants from the National Natural Science Foundation of China (82170699, 81870469 to Yanggang Yuan), “PRO•Run” Fund of the Nephrology Group of CEBM (KYJ202206--0003-6 to Yanggang Yuan), Project of clinical capability improvement of Jiangsu Province Hospital, the “333 Project” of Jiangsu Province, the Six Talent Peaks Project in Jiangsu Province (WSN-010 to Yanggang Yuan), Postgraduate Research & Practice Innovation Program of Jiangsu Province (JX10213856 to Meng Zhou), and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institution.

Disclosure

The authors declare that they have no competing interests.