A potential role for adipose tissue eosinophils in allergy and asthma.

Abstract

Abstract Allergy can take many forms, but a mutual trait is the hypersensitive immune response to what the body detects as foreign. A common form of airway allergy is asthma, which affects >235 million people worldwide and is the most common chronic disease among children. Interestingly, obese individuals have a staggering 92% increased risk of asthma, displaying enhanced asthmatic symptoms, airway hyper-responsiveness, & atopy. Due to the clinical correlation between obesity & asthma, scientific endeavors have sought to explain the causality. Studies have shown adipokines secreted from adipose tissue (AT) can have either pro- or anti-inflammatory effects on the lungs. Furthermore, diet-induced obesity increases migration of eosinophils from bone marrow to the lung, as well as delays exit from the airway epithelium to the lumen. Curiously, investigators have tried to understand the correlative link between asthma & obesity without closely examining the AT itself. Our data shows for the first time that AT mounts a hypereosinophilic state upon repeated exposure to a foreign substance (i.e. a hallmark of allergy & asthma in lung); increasing eosinophils from ~5% to 60% of AT leukocytes in obese mice. A single exposure does not elicit an eosinophilic response, potentially suggesting a role for the adaptive immune system. We found that obesity increased sensitivity of this immune response. Furthermore, the surge in AT eosinophils was dependent on IL33, a required cytokine for eosinophilic accumulation in lung during allergy. We are determining if other classic indicators of allergy are present in AT of our model. Ultimately, we hope to elucidate whether AT & lung act within a feedback loop that contributes to the incidence/severity of allergy & asthma.