Deep Immune and RNA Profiling Revealed Distinct Circulating CD163+ Monocytes in Diabetes-Related Complications

CD163, a scavenger receptor with anti-inflammatory function expressed exclusively on monocytes/macrophages, is dysregulated in cases of diabetes complications. This study aimed to characterize circulating CD163+ monocytes in the presence (D^+Comps) or absence (D^-Comps) of diabetes-related complications. RNA-sequencing and mass cytometry were conducted on CD163+ monocytes in adults with long-duration diabetes and D^+Comps or D^-Comps. Out of 10,868 differentially expressed genes identified between D^+Comps and D^-Comps, 885 were up-regulated and 190 were down-regulated with a ≥ 1.5-fold change. In D^+Comps, 'regulation of centrosome cycle' genes were enriched 6.7-fold compared to the reference genome. <i>MIR27A, MIR3648-1,</i> and <i>MIR23A</i>, the most up-regulated and <i>CD200R1</i>, the most down-regulated gene, were detected in D^+Comps from the list of 75 'genes of interest'. CD163+ monocytes in D^+Comps had a low proportion of recruitment markers CCR5, CD11b, CD11c, CD31, and immune regulation markers CD39 and CD86. A gene-protein network identified down-regulated <i>TLR4</i> and CD11b as 'hub-nodes'. In conclusion, this study reports novel insights into CD163+ monocyte dysregulation in diabetes-related complications. Enriched centrosome cycle genes and up-regulated <i>miRNAs</i> linked to apoptosis, coupled with down-regulated monocyte activation, recruitment, and immune regulation, suggest functionally distinct CD163+ monocytes in cases of diabetes complications. Further investigation is needed to confirm their role in diabetes-related tissue damage.