UC Riverside finds six eosinophil states in mouse fat tissue that differ by sex and RELMα status

Researchers at the University of California, Riverside, have described six transcriptionally distinct states of eosinophils in the adipose tissue of mice, according to a study in PNAS Nexus. The relative abundance of these clusters differs by sex, helminth infection and RELMα status oup.comPNAS Nexusoup.comOpen source ↗. Eosinophils are immune cells best known for their role in allergies and asthma, and they were long thought to perform a relatively narrow range of functions.

Six eosinophil states in fat tissue

The team, co-led by Meera Nair and Adam Godzik, used single-cell transcriptional profiling to examine adipose eosinophils at higher resolution. The study builds on an earlier functional work showing that the protein RELMα and eosinophils contribute to the protection of female mice from obesity induced by a high-fat diet.

Adipose tissue from females and from helminth-infected mice was enriched for clusters with type 2 and homeostatic transcriptional programs. Males and RELMα-deficient mice had more cells in inflammatory clusters associated with MHCII. According to the authors, in males on a high-fat diet these populations showed gene-expression patterns that suggest weaker protective functions.

Spectral flow cytometry and in situ hybridization in adipose tissue independently supported the heterogeneity of eosinophils and the candidate chemokine-receptor interactions oup.comPNAS Nexusoup.comOpen source ↗.

Communication with macrophages

The predicted macrophage-eosinophil communication networks also differed between groups. RELMα is a protein produced by macrophages, and in female mice a protective eosinophil population communicated more effectively with macrophages. The authors state that the link between eosinophils and obesity depends not only on the number of cells but also on their functional characteristics and on how they interact with other immune cells.

Single-cell regulatory network inference identified transcription factor regulons specific to individual clusters, including regulatory programs that differ by sex and are enriched under a high-fat diet.

The data provide a framework for describing eosinophil heterogeneity within the previously established RELMα-macrophage-eosinophil axis. The candidate transcriptional and communication programs still require functional testing. Eosinophils have been detected in the fat tissue of people with obesity, but it has not been established whether they perform the same protective or inflammatory functions as in mice. The group is now developing three-dimensional adipose organoids to study how eosinophils interact with fat cells and macrophages.