Weight gain alters adiponectin receptor 1 expression on lung-resident Foxp3+ Helios+ regulatory T cells: Implications during allergic airway inflammation?

Abstract

Background: Adiponectin is an anti-inflammatory adipokine that acts through adiponectin receptors 1 and 2 (AdipoR1/AdipoR2). We have found that AdipoR1 is expressed on regulatory T-cells (Tregs) in adipose tissue, but the expression on lung Tregs is still unknown. Even more, the effect of allergic inflammation during obesity on lung and adipose Tregs and their AdipoR1 expression remains unexplored. Aims: To determine the AdipoR1 expression in lung and adipose tissue Tregs upon allergic inflammation and during weight gain. Methods: Male C57BL/6 mice were fed with a high fat diet (HFD) up to 15 (overweight) or 26 (obesity) weeks of age. Overweight and obese mice were sensitized and subsequently challenged with ovalbumin during five days. Overweight and obese mice were used as non-allergic controls. Tregs and AdipoR1 were evaluated in lung and adipose tissue by flow cytometry. Results: HFD resulted in significant weight gain in both non-allergic and allergic mice. The majority of Foxp3+ Tregs in both lung and adipose tissue expressed Helios which were significantly reduced upon weight gain in both, allergic and non-allergic mice. Interestingly, the AdipoR1 expression in both, Treg and non-Treg cells, was reduced in adipose tissue, but increased in lung upon weight gain. Importantly, no changes were found in AdipoR1 expression on Tregs between allergic and non-allergic mice. Conclusion: Our data show a reduction of Tregs in lung and adipose tissue during obesity. Weight gain alters the AdipoR1 expression on Treg and non-Treg cells in lung and adipose tissue and thus possibly affects the local inflammation.