Airway inflammation in a murine model of asthma evokes adipose Type 2 immune response and eosinophil recruitment in visceral fat 4079

Description The localized impact of inflammation and Type 2 (Th2) cytokines on the airway in murine asthma models has been well documented. However, the systemic impact of lung inflammation on other organs remains poorly understood. It is known that Th2 immunity plays regulatory roles in adipose tissue homeostasis; however, it is unknown whether lung Th2 inflammation impacts adipose tissue. In this study, we utilized asthma models in lean, metabolically healthy, mice to investigate the systemic nature of lung inflammation. Using flow cytometry, scRNA-seq, and tissue RNA expression analysis, we found that visceral adipose tissue (VAT) showed an increase in eosinophils and expression of Th2 markers (i.e., IL-4, IL-5, IL-33, and eotaxin CCL11) mirroring allergic lung inflammation. Serum analysis showed that lung allergic inflammation increases circulating levels of hormones glucagon-like peptide-1 (GLP-1), pancreatic polypeptide, peptide YY, and resistin. Our data shows that IL-5 promotes CCL11/FGF21-mediated eosinophil recruitment and activation within the VAT. This co-occurs with IL-4 production by eosinophils and GLP-1 production in the small intestine. Cytokines and hormones synergistically promote white adipose tissue beiging and lipolysis in inflammation. Our data elucidates a novel multi-organ communication pathway between the lung, VAT, and small intestine that could be necessary to maintain systemic energy homeostasis sustaining energy-expensive resolution/repair processes. Funding Sources Supported by NIH/NIAID grant R01AI127783; Ernest S. Bazley Foundation.