Lung Regulatory T Cells Express Adiponectin Receptor 1: Modulation by Obesity and Airway Allergic Inflammation.

Mikael Adner,Apostolos Bossios,Jan Lötvall,Kristina Johansson,Carina Malmhäll,Patricia Ramos-Ramírez

doi:10.3390/ijms21238990

Abstract

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.

Highlights

Obesity is recognized by the World Health Organization (WHO) as an epidemic, as worldwide obesity has nearly tripled since 1975, reaching 650 million adults in 2016 [1]
Using models of diet-induced obesity (DIO) and airway allergic inflammation, we showed that obesity resulted in a reduction in the adiponectin receptor 1 (AdipoR1) expression
Airway allergic inflammation in lean mice resulted in a reduced expression, while for airway allergic inflammation combined with obesity, the AdipoR1 expression followed the obesity pattern

Summary

Introduction

Obesity is recognized by the World Health Organization (WHO) as an epidemic, as worldwide obesity has nearly tripled since 1975, reaching 650 million adults in 2016 [1]. Most of the body’s physiological functions are negatively affected by obesity, and obesity increases the risk of developing multiple diseases resulting in a public health threat [2]. A link between obesity and asthma was attributed to the excessive accumulation of adipose tissue, which may promote systemic inflammation that reaches distant sites, such as the lungs [4]. Adipose tissue is infiltrated by various immune cells that contribute to low-grade inflammation, generating a systemic effect [6]. It was recently demonstrated that adipose tissue is present within the airway wall and is related to BMI and the number of inflammatory cells in obstructive airway diseases [7]

Objectives

Methods

Results

Conclusion