Eosinophils are leukocytes with broad roles in tissue homeostasis and innate immunity. Eosinophils are important in host defense against helminth infection but are inappropriately activated in pathologies such as asthma and esophagitis. However, eosinophils also reside within normal healthy adipose tissue.
Adipose tissue-resident eosinophils play homeostatic roles and, along with other adipose tissue-resident immune cells, regulate the activation of beige adipocytes. Beige adipocytes residing within white adipose tissue burn fuels to generate heat, by a process called thermogenesis, and therefore may be able to be harnessed to reduce obesity by burning rather than storing excess fuels. We recently uncovered gene regulatory mechanisms in mice that allow adipose tissue-resident eosinophils to secrete molecules important for beige fat activation and prevention of weight gain.
Given the potential of adipose tissue-resident eosinophils to drive beige fat activation and weight loss, we sought to generate a better understanding of these cells. We performed bulk RNA-seq in mouse FACS-isolated adipose tissue-resident eosinophils, for the first time, and compared gene expression to blood eosinophils. We found a unique transcriptional landscape in adipose tissue-resident eosinophils that is distinct from blood eosinophils in circulation and also distinct from previously published transcriptomes of lung, colon and bone marrow eosinophils. Differential gene expression of surface receptors, chemokines and associated genes suggest that adipose tissue-resident eosinophils functionally adapt to their tissue niche. We also performed an analysis of transcription factors that may drive this adaptation which identified the importance of KLF family, Fos/Jun families and CEBP families in regulating the transcriptome of adipose tissue-resident eosinophils.
We are now working to further define the transcription factor network that drives this unique gene expression profile of adipose tissue-resident eosinophils. We are also testing whether novel adipose tissue-resident eosinophil secreted proteins, that we identified in our RNA-seq data, are able to induce beiging and energy expenditure and may present novel targets for obesity.