In fat tissue from female mice, one kind of immune cell appeared to help keep inflammation in check—while similar cells in males tended to show a more harmful pattern. The finding, from scientists at the University of California, Riverside, points to one reason obesity may affect males and females differently.
The study, published in PNAS Nexus, examined eosinophils, immune cells best known for their role in asthma and allergies. Researchers have often treated eosinophils as a fairly uniform group. But the UCR team found that fat tissue held several distinct types, with different gene activity and possible roles in the body. That matters because obesity is linked to inflammation and metabolic problems, and immune cells may help shape how those effects develop.
Led by biomedical scientists Meera Nair and Adam Godzik, the team used high-resolution single-cell sequencing to identify six eosinophil populations in mouse fat tissue. The method lets researchers examine the activity of individual cells rather than averaging signals across a large sample. The six groups had different patterns of gene expression, suggesting they may not all do the same job.
The differences were also tied to sex. Female mice had a population of eosinophils that communicated more effectively with macrophages, another type of immune cell in fat. This interaction may support a healthier metabolic environment. In male mice fed a high-fat diet, eosinophils more often showed a pro-inflammatory pattern and a less protective gene signature.
The researchers also singled out RELM alpha, a protein made by macrophages. In female mice, the protein appeared to help stabilize communication between macrophages and eosinophils. Earlier experiments by the team found protective effects when RELM alpha was given to mice, adding support to the idea that this signal may help regulate immune activity in fat tissue.
The results suggest that the effects of eosinophils depend not simply on how many are present, but on what kinds they are and how they interact with other cells. “Their functional characteristics and how they communicate with other immune cells are also critical,” said Rebecca E. Ruggiero-Ruff, a postdoctoral researcher in Nair’s lab and a co-first author of the paper.
The findings are not yet a guide to treatment in people. Eosinophils have been found in the fat tissue of people with obesity, but their exact roles there remain unclear. Nair said more research is needed before the mouse results can be applied to human health. The work also highlights why studies of immune-based treatments should examine males and females separately: a drug may trigger different pathways or effects in each.
Next, the team plans to test whether the protective cell interactions can be recreated in human models. Godzik and colleagues are developing three-dimensional adipose organoids—lab structures that mimic some features of fat tissue—to study how eosinophils interact with fat cells. If those models work, they could help researchers explore whether changing communication among immune cells can encourage healthier tissue responses, while keeping the differences between patients in view.