Identification and validation of tolerogenic dendritic cells-related biomarkers in diabetic retinopathy

ObjectiveDiabetic retinopathy (DR) is a primary microvascular complication of diabetes. Its pathogenesis is associated with chronic inflammation and immune responses. While tolerogenic dendritic cells (tolDCs) are critical for suppressing excessive inflammation and maintaining immune homeostasis, their function in DR is not well characterized. This study aims to identify tolDCs-related biomarkers and elucidate their underlying mechanisms in DR through integrated bioinformatics and clinical validation. MethodsAll data used in this study were obtained from public databases. Biomarkers were identified through differential analysis, machine learning, and expression validation. Subsequently, enrichment analysis and immune infiltration were used to investigate the functional mechanisms of the biomarkers. Finally, clinical peripheral blood specimens were obtained for validation using reverse transcription-quantitative PCR (RT-qPCR). ResultsA total of 2,096 differentially expressed genes (DEGs)1 were identified between DR and control groups. A total of 6,267 tolDCs-related genes were identified. After that, 51 key genes were selected. A total of 2 biomarkers, TFEC and CHMP2A, were identified through machine learning and expression validation selecting. GSEA results demonstrated TFEC enrichment in 994 pathways, among which was "Cytoplasmic Ribosomal Proteins." CHMP2A was enriched in 748 pathways, including "tRNA Processing." The pathways enriched by both TFEC and CHMP2A included "apoptosis," "VEGFA-VEGFR2 signaling," and "signaling by VEGF," among others. A total of 8 differential immune cell types were identified, including resting mast cells. TFEC showed the strongest correlation with activated NK cells (correlation coefficient (cor) = -0.49, p< 0.001), CHMP2A with resting mast cells (cor = 0.49, p< 0.001). RT-qPCR analysis revealed a significant upregulation of TFEC and downregulation of CHMP2A in the DR group, aligning with the bioinformatics findings. ConclusionTFEC and CHMP2A were identified as biomarkers and were involved in the development of DR through tolDCs.