CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity. Issue 6 (11th December 2015)

• Record Type: Journal Article
• Authors: Morris, David L; Oatmen, Kelsie E; Mergian, Taleen A; Cho, Kae Won; DelProposto, Jennifer L; Singer, Kanakadurga; Evans-Molina, Carmella; O'Rourke, Robert W; Lumeng, Carey N
• Is Part Of: Journal of leukocyte biology. Volume 99:Issue 6(2016)
• Page Start: 1107
• Page End: 1119
• Publication Date: 2015-12-11
• Subjects: inflammation -- antigen presenting cells (APC) -- CD40L; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.3A0115-009R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : CD40-deficient mice fail to induce conventional CD4 + cells in adipose tissue associated with decreased markers of antigen presentation in ATMs. Abstract: Obesity activates both innate and adaptive immune responses in adipose tissue, but the mechanisms critical for regulating these responses remain unknown. CD40/CD40L signaling provides bidirectional costimulatory signals between antigen-presenting cells and CD4 + T cells, and CD40L expression is increased in obese humans. Therefore, we examined the contribution of CD40 to the progression of obesity-induced inflammation in mice. CD40 was highly expressed on adipose tissue macrophages in mice, and CD40/CD40L signaling promoted the expression of antigen-presenting cell markers in adipose tissue macrophages. When fed a high fat diet, Cd40 -deficient mice had reduced accumulation of conventional CD4 + T cells (Tconv : CD3 + CD4 + Foxp3 − ) in visceral fat compared with wild-type mice. By contrast, the number of regulatory CD4 + T cells (Treg : CD3 + CD4 + Foxp3 + ) in lean and obese fat was similar between wild-type and knockout mice. Adipose tissue macrophage content and inflammatory gene expression in fat did not differ between obese wild-type and knockout mice; however, major histocompatibility complex class II and CD86 expression on adipose tissue macrophages was reduced in visceral fat from knockout mice. Similar results were observed in chimeric mice with hematopoietic Cd40 -deficiency. Nonetheless, neither whole body nor hematopoietic disruption of CD40 ameliorated obesity-induced insulin resistance in mice. In human adipose tissue, CD40 expression was positively correlated with CD80 and CD86 expression in obese patients with type 2 diabetes. These findings indicate that CD40 signaling in adipose tissue macrophages regulates major histocompatibility complex class II and CD86 expression to control the expansion of CD4 + T cells; however, this is largely dispensable for the development of obesity-induced inflammation and insulin resistance in mice.