Over one third of Australians are overweight or obese. Heart disease, Type II Diabetes Mellitus, and obesity-associated cancers make obesity the leading cause of death or disability. Obesity is propagated by chronic inflammation, which is executed by pro-inflammatory immune cells that reside in the adipose tissue. On the contrary, in lean healthy individuals’ metabolic homeostasis is sustained by a population of regulatory homeostatic immune cells. One such beneficial adipose-resident immune cell population are eosinophils. Eosinophils have been found to support insulin sensitivity, glucose tolerance, and promote thermogenesis, a fat-burning metabolic state.
Due to high RNase content, and low cell numbers, eosinophils are often excluded from transcriptional analyses of adipose-resident immune cells. We have performed the first RNA-seq analysis of adipose-resident eosinophils, identifying these cells as transcriptionally distinct, with thousands of differentially expressed genes when compared to eosinophils from peripheral blood. From this profile we have identified transcription factors which may be regulators of adipose-resident eosinophils. Using CRISPR/Cas9 genome editing, we have produced knockout eosinophil cell lines for these transcription factors. RNA-seq analysis of these cells suggests that one of these transcription factors is a major repressor of inflammatory gene expression, with potential roles in activating metabolically beneficial genes. We propose that identifying the regulators of adipose-resident eosinophil pathways will allow us to augment these cells’ natural ability to sustain metabolic homeostasis, allowing for the exploration of new therapeutic options for obesity.