Obesity is an epidemic of global concern, with nearly half of all adults being overweight. Western diet, rich in fat and lipids and poor in aryl hydrocarbon receptor (AHR) ligands, acts on the adipose tissue and affects cellular programming and cellular communication. We aim to uncover key questions on the interplay between adipose tissue immune cells. Eosinophils, through effects on other immune and stromal populations, are key players in adipose tissue physiology and counteract diet-induced metaflammation. In the second funding period we will study if eosinophils and their crosstalk with T_reg cells are a major determinant of the local and systemic inflammatory response driving metaflammation. Adipose tissue eosinophils have a distinct transcriptional signature when compared to blood eosinophils or those from other tissues, and our preliminary data suggest a role for AHR in this process. We hypothesize that tissue eosinophils can be reprogrammed on the epigenetic, transcriptional, and functional level by diet, in particular AHR ligands. This in turn impacts T_reg cells and affects the broader immune and metabolic functions of the tissues, opening up potential new therapeutic avenues to modulate metaflammation. Our project will answer how dietary manipulation of AHR activity changes the interplay of eosinophils and T_reg cells and their role in controlling WAT homeostasis and metaflammation. We will further study how this T_reg cell-eosinophil interaction shapes the tissue response to HFD-induced metaflammation. Results of this study may provide new rationales for future interventions in Western diet-induced metaflammation