Blood and adipose-resident eosinophils are defined by distinct transcriptional profiles.

Eosinophils are granular leukocytes of the innate immune system that play important functions in host defense. Inappropriate activation of eosinophils can occur in pathologies such as asthma and esophagitis. However, eosinophils also reside within adipose tissue, where they play homeostatic roles and are important in the activation of thermogenic beige fat. Here we performed bulk RNA sequencing in mouse adipose tissue-resident eosinophils isolated from both subcutaneous and gonadal depots, for the first time, and compared gene expression to blood eosinophils. We found a predominantly conserved transcriptional landscape in eosinophils between adipose depots that is distinct from blood eosinophils in circulation. Through exploration of differentially expressed transcription factors and transcription factors with binding sites enriched in adipose-resident eosinophil genes, we identified KLF, CEBP, and Fos/Jun family members that may drive functional specialization of eosinophils in adipose tissue. These findings increase our understanding of tissue-specific eosinophil heterogeneity, with implications for targeting eosinophil function to treat metabolic disorders such as obesity.

Shades of white: new insights into tissue-resident leukocyte heterogeneity.

Populations of white blood cells (leukocytes) have been found in tissues and organs across the body, in states of both health and disease. The role leukocytes play within these tissues is often highly contested. For many leukocytes, there are studies outlining pro-inflammatory destructive functions, while other studies provide clear evidence of anti-inflammatory homeostatic activities of leukocytes within the same tissue. We discuss how this functional dissonance can be explained by leukocyte heterogeneity. Although cell morphology and surface receptor profiles are excellent methods to segregate cell types, the true degree of leukocyte heterogeneity that exists can only be appreciated by studying the variable and dynamic gene expression profile. Unbiased single-cell RNA sequencing profiling of tissue-resident leukocytes is transforming the way we understand leukocytes across health and disease. Recent investigations into adipose tissue-resident leukocytes have revealed unprecedented levels of heterogeneity among populations of macrophages. We use this example to pose emerging questions regarding tissue-resident leukocytes and review what is currently known (and unknown) about the diversity of tissue-resident leukocytes within different organs.

EoTHINophils: Eosinophils as key players in adipose tissue homeostasis.

Eosinophils are granular cells of the innate immune system that are found in almost all vertebrates and some invertebrates. Knowledge of their wide-ranging roles in health and disease has largely been attained through studies in mice and humans. Although eosinophils are typically associated with helminth infections and allergic diseases such as asthma, there is building evidence that beneficial homeostatic eosinophils residing in specific niches are important for tissue development, remodelling and metabolic control. In recent years, the importance of immune cells in the regulation of adipose tissue homeostasis has been a focal point of research efforts. There is an abundance of anti-inflammatory innate immune cells in lean white adipose tissue, including macrophages, eosinophils and group 2 innate lymphoid cells, which promote energy homeostasis and stimulate the development of thermogenic beige adipocytes. This review will evaluate evidence for the role of adipose-resident eosinophils in local tissue homeostasis, beiging and systemic metabolism, highlighting where more research is needed to establish the specific effector functions that adipose eosinophils perform in response to different internal and external cues.