Greg 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.
Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
Int J Mol Sci. 2024 Sep 19;25(18):10094. 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.
CD163 是一种仅在单核细胞/巨噬细胞上表达的具有抗炎功能的清道夫受体,在糖尿病并发症中失调。本研究旨在描述存在(D)或不存在(D)糖尿病相关并发症时循环 CD163+单核细胞的特征。对长期患有糖尿病且存在(D)或不存在(D)糖尿病相关并发症的成年人的 CD163+单核细胞进行 RNA 测序和质谱流式细胞术分析。在 D 和 D 之间鉴定的 10868 个差异表达基因中,有 885 个基因上调,190 个基因下调,变化倍数≥1.5。与参考基因组相比,D 中“中心体周期调节”基因富集了 6.7 倍。和,上调最明显的基因和,下调最明显的基因,从 75 个“感兴趣的基因”列表中检测到 D 中存在。D 中的 CD163+单核细胞的募集标志物 CCR5、CD11b、CD11c、CD31 和免疫调节标志物 CD39 和 CD86 的比例较低。基因-蛋白网络鉴定出下调的和 CD11b 为“枢纽节点”。总之,本研究报告了糖尿病相关并发症中 CD163+单核细胞失调的新见解。丰富的中心体周期基因和上调的与细胞凋亡有关,加上下调的单核细胞激活、募集和免疫调节,表明在糖尿病并发症中存在功能不同的 CD163+单核细胞。需要进一步研究来确认它们在糖尿病相关组织损伤中的作用。