CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity
dc.contributor.author | Morris, David L. | |
dc.contributor.author | Oatmen, Kelsie E. | |
dc.contributor.author | Mergian, Taleen A. | |
dc.contributor.author | Cho, Kae Won | |
dc.contributor.author | DelProposto, Jennifer L. | |
dc.contributor.author | Singer, Kanakadurga | |
dc.contributor.author | Evans-Molina, Carmella | |
dc.contributor.author | O’Rourke, Robert W. | |
dc.contributor.author | Lumeng, Carey N. | |
dc.contributor.department | Medicine, School of Medicine | en_US |
dc.date.accessioned | 2017-12-15T14:19:00Z | |
dc.date.available | 2017-12-15T14:19:00Z | |
dc.date.issued | 2016-06 | |
dc.description.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. | en_US |
dc.eprint.version | Final published version | |
dc.identifier.citation | Morris, D. L., Oatmen, K. E., Mergian, T. A., Cho, K. W., DelProposto, J. L., Singer, K., … Lumeng, C. N. (2016). CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity. Journal of Leukocyte Biology, 99(6), 1107–1119. http://doi.org/10.1189/jlb.3A0115-009R | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/14830 | |
dc.language.iso | en_US | en_US |
dc.publisher | Society for Leukocyte Biology | en_US |
dc.relation.isversionof | 10.1189/jlb.3A0115-009R | en_US |
dc.relation.journal | Journal of Leukocyte Biology | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | CD40L | en_US |
dc.subject | Antigen presenting cells (APC) | en_US |
dc.subject | Inflammation | en_US |
dc.title | CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity | en_US |
dc.type | Article | en_US |
ul.alternative.fulltext | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4952010/ | en_US |
Files
Original bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity.pdf
- Size:
- 1.57 MB
- Format:
- Adobe Portable Document Format
- Description:
- Main article
License bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- license.txt
- Size:
- 1.99 KB
- Format:
- Item-specific license agreed upon to submission
- Description: