Alterations of Scavenger Receptor CD163 in Diabetes Complications

Abstract

The progressive and unresolving nature of diabetes complications cause irreversible tissue damage. Inflammation is implicated in diabetes complications at tissue and systemic level. Anti-inflammatory haemoglobin-haptoglobin scavenger receptor, CD163, is decreased on monocytes and may be implicated diabetes complications progression. We aimed to investigate whether levels of circulating CD163+ monocytes and sCD163 are impacted in, and can act as a mediator or biomarker in diabetes complications and disease progression; and also investigate the regulation of CD163. A systematic review surveyed CD163 and sCD163 levels; ELISA quantified plasma sCD163; CyTOF used to phenotype circulating white blood cells (WBCs), including CD163+ monocytes and RNA-seq, examined the transcriptome of CD163+ monocytes. Multiplex immunoassay quantified cytokines, chemokines and MMPs in individuals with and without diabetes complications. In a diabetes cohort with NAFLD, plasma sCD163 was increased and implicated in NASH progression with clinical utility. The transcriptome and immunophenotype profile of CD163+ monocytes revealed a reduced capacity for trans-endothelial migration, monocyte activation and dysregulated interaction with adaptive immune system, in diabetes complications. WBCs were different in diabetes complications. Plasma cytokines IL-10 and IL-5 were increased in diabetes complications, but not correlated with CD163+ monocytes or sCD163 levels. Plasma MMP-2, -7 and -10 were correlated with sCD163 levels in individuals with diabetes complications. Diabetes complications indicates transcriptomic changes of CD163+ monocytes, resulting in decreased CD163+ circulating monocytes, as does the proteolytic action of MMP-2, -7 and 10. Plasma sCD163 is a useful indicator of disease severity in diabetes complications. The phenotypes of the CD163+ monocytes and circulating WBCs are altered in diabetes complications, such that they favour the progression of chronic complications.