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

• Published in: International journal of molecular sciences 2024-09, Vol.25 (18), p.10094
• Main Authors: Siwan, Elisha, Wong, Jencia, Brooks, Belinda A, Shinko, Diana, Baker, Callum J, Deshpande, Nandan, McLennan, Susan V, Twigg, Stephen M, Min, Danqing
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens, CD - genetics; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - genetics; Antigens, Differentiation, Myelomonocytic - metabolism; Biomarkers; Cardiovascular disease; CD163; Chemokines; complications; Complications and side effects; Cytokines; Development and progression; Diabetes; Diabetes Complications - blood; Diabetes Complications - genetics; Diabetes Complications - immunology; diabetes mellitus; Diabetic angiopathies; Diabetic nephropathies; Female; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Genes; Health aspects; Humans; Inflammation; Male; MicroRNAs; MicroRNAs - genetics; Middle Aged; Monocytes; Monocytes - immunology; Monocytes - metabolism; Orexin Receptors - genetics; Orexin Receptors - metabolism; Physiological aspects; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Risk factors; scavenger receptor
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms251810094

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 ) or absence (D ) of diabetes-related complications. RNA-sequencing and mass cytometry were conducted on CD163+ monocytes in adults with long-duration diabetes and D or D . Out of 10,868 differentially expressed genes identified between D and D , 885 were up-regulated and 190 were down-regulated with a ≥ 1.5-fold change. In D , 'regulation of centrosome cycle' genes were enriched 6.7-fold compared to the reference genome. and , the most up-regulated and , the most down-regulated gene, were detected in D from the list of 75 'genes of interest'. CD163+ monocytes in D 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 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 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.