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

Elisha Siwan1, Jencia Wong1,2, Belinda A Brooks2

  • 1Greg Brown Diabetes and Endocrine Research Laboratory, Sydney Medical School (Central), Faculty of Medicine and Health, Charles Perkin Centre, The University of Sydney, Sydney, NSW 2006, Australia.

Insights

Diabetes complications alter CD163+ monocytes, impacting immune regulation and cell cycle genes. These findings reveal distinct monocyte functions in diabetic patients with complications, suggesting a role in tissue damage.

Area of Science:

  • Immunology
  • Endocrinology
  • Molecular Biology

Background:

  • CD163, a scavenger receptor with anti-inflammatory properties, is expressed on monocytes/macrophages.
  • Dysregulation of CD163 is observed in diabetes complications.
  • Understanding CD163+ monocyte characteristics is crucial for diabetes research.

Purpose of the Study:

  • To characterize circulating CD163+ monocytes in adults with long-duration diabetes.
  • To compare CD163+ monocytes between diabetic patients with (D+Comps) and without (D-Comps) diabetes-related complications.

Main Methods:

  • RNA-sequencing and mass cytometry were performed on CD163+ monocytes.
  • Analysis focused on gene expression and protein markers in D+Comps versus D-Comps groups.
  • Gene-protein network analysis was utilized to identify key regulatory nodes.

Main Results:

  • 10,868 differentially expressed genes were identified between D+Comps and D-Comps.
  • Genes related to 'regulation of centrosome cycle' were significantly enriched in D+Comps.
  • CD163+ monocytes in D+Comps showed reduced expression of recruitment and immune regulation markers (e.g., CCR5, CD11b, CD39, CD86).

Conclusions:

  • CD163+ monocytes exhibit distinct functional profiles in diabetes complications.
  • Enriched centrosome cycle genes and altered miRNA expression suggest changes in cell cycle and apoptosis.
  • Down-regulated monocyte activation and recruitment markers may contribute to diabetes-related tissue damage.

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