Weight Gain Alters Adiponectin Receptor 1 Expression on Adipose Tissue‐Resident Helios+ Regulatory T Cells

• Published in: Scandinavian journal of immunology 2016-04, Vol.83 (4), p.244-254
• Main Authors: Ramos‐Ramírez, P., Malmhäll, C., Johansson, K., Lötvall, J., Bossios, A.
• Format: Article
• Language: English
• Subjects: Adipose Tissue - cytology; Adipose Tissue - immunology; Adipose Tissue - metabolism; Animals; Body Weight - immunology; Diet, High-Fat; DNA-Binding Proteins - metabolism; Inflammation - immunology; Inflammation - pathology; Male; Mice; Mice, Inbred C57BL; Obesity - immunology; Receptors, Adiponectin - biosynthesis; Spleen - cytology; Spleen - immunology; Spleen - metabolism; T-Lymphocytes, Regulatory - immunology; Transcription Factors - metabolism; Weight Gain - immunology
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/sji.12419

Adipose tissue produces multiple mediators that modulate the immune response. Adiponectin is an adipocyte‐derived cytokine that exhibits metabolic and anti‐inflammatory effects. Adiponectin acts through binding to adiponectin receptor 1 and 2 (AdipoR1/AdipoR2). AdipoR1 is ubiquitously expressed, whereas AdipoR2 is restricted to skeletal muscle and liver. AdipoR1 expression has been reported on a small percentage of T cells; nevertheless, it is still unknown whether Foxp3+ regulatory T cells (Tregs) express AdipoR1. Recently, it has been shown that Tregs accumulate in adipose tissue and that they play a potential role in modulating adipose tissue inflammation. Our aim was to evaluate AdipoR1 expression in adipose tissue‐resident Tregs and to evaluate the effect of weight gain on this expression. Male C57BL/6 mice were fed with a high‐fat diet for 14 weeks (to develop overweight) or 21 weeks (to develop obesity). Mice on a standard diet were used as age‐matched controls. Helios expression was evaluated as a marker to discriminate thymic‐derived from peripherally induced Tregs. The majority of Tregs in both adipose tissue and the spleen expressed Helios. Adipose tissue Tregs expressed higher levels of AdipoR1 than Tregs in the spleen. AdipoR1 expression on adipose tissue Helios+ Tregs was negatively correlated with epididymal fat. Overall, we show that AdipoR1 is expressed on adipose tissue‐resident Tregs, mainly Helios+ Tregs, and that this expression is dependent on weight and fat accumulation. Because both adiponectin and Tregs play roles in anti‐inflammatory mechanisms, our data propose a new mechanism through which weight gain might alter immunoregulation.