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

Int J Mol Sci. 2024 Sep 19;25(18):10094. doi: 10.3390/ijms251810094.

Abstract

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. MIR27A, MIR3648-1, and MIR23A, the most up-regulated and CD200R1, 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 TLR4 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 miRNAs 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.

Keywords: CD163; complications; diabetes mellitus; inflammation; monocytes; scavenger receptor.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD* / genetics
  • Antigens, CD* / metabolism
  • Antigens, Differentiation, Myelomonocytic* / genetics
  • Antigens, Differentiation, Myelomonocytic* / metabolism
  • Biomarkers
  • Diabetes Complications / blood
  • Diabetes Complications / genetics
  • Diabetes Complications / immunology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Humans
  • Male
  • MicroRNAs* / genetics
  • Middle Aged
  • Monocytes* / immunology
  • Monocytes* / metabolism
  • Orexin Receptors / genetics
  • Orexin Receptors / metabolism
  • Receptors, Cell Surface* / genetics
  • Receptors, Cell Surface* / metabolism

Substances

  • Antigens, CD
  • CD163 antigen
  • Receptors, Cell Surface
  • Antigens, Differentiation, Myelomonocytic
  • MicroRNAs
  • Orexin Receptors
  • CD200R1 protein, human
  • Biomarkers