Changes in the Adipose Tissue Expression of CD86 Costimulatory Ligand and CD163 Scavenger Receptor in Obesity and Type-2 Diabetes: Implication for Metabolic Disease

Sardar Sindhu, Reeby Thomas

Abstract

Background: The CD86 costimulatory ligand and CD163 scavenger receptor are expressed on monocytes/macrophages. However, modulations in the expression of these immune regulatory receptors in metabolic disease remain unclear. We, therefore, compared the adipose tissue expression of CD86/CD163 and signature inflammatorycytokines/chemokines in non-diabetic and diabetic individuals. Methods: Subcutaneous adipose tissue biopsies were collected from 57 non-diabetics and 46 diabetics classified based on body mass index as obese, overweight and lean and the expression of CD86/CD163 was assessed by quantitative RT-PCR, immunohistochemistry/ confocal microscopy. Results: The data show that CD86 and CD163 gene expression was elevated in non-diabetic obese individuals as compared with their lean counterparts (P [CD86] = 0.0035; P [CD163] = 0.0028). As expected, CD86 and CD163 protein expression was also found to be elevated in the adipose tissue samples of obese individuals. The CD86 gene expression in non-diabetic and diabetic individuals correlated positively (P<0.05) with that of TNF-α (r [non-diabetic] = 0.26; r [diabetic] = 0.49), IL-18 (r [non-diabetic] = 0.67; r [diabetic] = 0.63), and IL-8 (r [non-diabetic] = 0.38; r [diabetic] = 0.33). The CD86 gene expression correlated significantly with that of IL-23 and IP-10 in non-diabetic individuals. The CD86 gene expression also correlated with glycated hemoglobin (r [diabetic] = 0.38; P = 0.007). In parallel, CD163 gene expression also correlated positively (P<0.05) with TNF-α (r [non-diabetic] = 0.35; r [diabetic] = 0.38), IL-18 (r [non-diabetic] = 0.72; r [diabetic] = 0.71), IL-23 (r [non-diabetic] = 0.28), and IL-8 (r [non-diabetic] = 0.58; r [diabetic] = 0.35). The adipose tissue expression of IL-18 independently predicted the expression of CD86 and CD163 both in non-diabetic and diabetic individuals. Conclusion: The adipose tissue expression of CD86 and CD163 is elevated in obesity and T2D which has consensus with inflammatory signatures and represents novel immune markers for metabolic inflammation.

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