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Published on: August 12, 2016
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.
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.
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