Krefting Research Centre, Department for Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
Institute of Environmental Medicine, Karolinska Institutet, SE-171 65 Stockholm, Sweden.
Int J Mol Sci. 2020 Nov 26;21(23):8990. doi: 10.3390/ijms21238990.
Regulatory T cells (Tregs) decrease in the adipose tissue upon weight gain, contributing to persistent low-grade inflammation in obesity. We previously showed that adipose tissue Tregs express the adiponectin receptor 1 (AdipoR1); however, the expression in lung Tregs is still unknown. Here, we aimed to determine whether Helios and Helios Treg subsets expressed AdipoR1 in the lungs of obese mice and whether different obesity grades affected the expression upon allergic lung inflammation. For diet-induced obesity (DIO), mice were fed a high-fat diet (HFD) for up to 15 weeks (overweight), 21 weeks (obesity), and 26 weeks (morbid obesity). Overweight and morbidly obese mice were sensitized and challenged with ovalbumin (OVA) to induce allergic lung inflammation. The AdipoR1 expression was reduced significantly in the lung Helios and Helios Tregs of obese mice compared with lean mice. Airway allergic inflammation showed reduced AdipoR1 expression in lung Foxp3 Tregs. Obesity significantly exacerbated the eosinophilic airway inflammation and reduced the number of Helios Tregs in lung and adipose tissue in the obesity-associated asthma model. Upon further weight gain, AdipoR1-expressing Tregs in the lungs of allergic mice were increased, whereas AdipoR1-expressing Tregs in adipose tissue were reduced. These data suggest that obesity-associated adipose tissue inflammation may exacerbate allergic inflammation by downregulating the AdipoR1 Tregs in the lungs.
调节性 T 细胞（Tregs）在体重增加时会减少脂肪组织中的数量，导致肥胖症中的持续低度炎症。我们之前曾表明脂肪组织中的 Tregs 表达脂联素受体 1（AdipoR1）；然而，肺 Tregs 中的表达仍然未知。在这里，我们旨在确定肥胖小鼠的肺组织中 Helios 和 Helios Treg 亚群是否表达 AdipoR1，以及不同肥胖程度是否会影响过敏肺炎症时的表达。对于饮食诱导的肥胖（DIO），将小鼠用高脂肪饮食（HFD）喂养长达 15 周（超重）、21 周（肥胖）和 26 周（病态肥胖）。对超重和病态肥胖的小鼠进行卵清蛋白（OVA）致敏和攻毒以诱导过敏性肺炎症。与瘦鼠相比，肥胖鼠肺中的 Helios 和 Helios Tregs 中 AdipoR1 的表达显著降低。气道过敏炎症显示肺 Foxp3 Tregs 中的 AdipoR1 表达减少。肥胖症在肥胖相关哮喘模型中显著加剧了嗜酸性气道炎症并减少了肺和脂肪组织中的 Helios Tregs 数量。随着体重进一步增加，过敏性小鼠肺中表达 AdipoR1 的 Tregs 增加，而脂肪组织中表达 AdipoR1 的 Tregs 减少。这些数据表明，与肥胖相关的脂肪组织炎症可能通过下调肺中的 AdipoR1 Tregs 来加重过敏炎症。
