Single-cell heterogeneity of adipose eosinophils is shaped by sex and RELMα and linked to macrophage communication networks in obesity
- 1Division of Biomedical Sciences, School of Medicine, University of California , Riverside; Riverside, CA 92521 ,
- 2Department of Biochemistry, Graduate Program in Biochemistry and Molecular Biology, College of Natural and Agricultural Sciences, University of California , Riverside; Riverside, California CA92521 ,
Abstract
Eosinophils are immune cells with terminal effector functions in type 2 immune responses, yet recent findings suggest that they exhibit functional plasticity and heterogeneity dependent on tissue-specific cues. Building on our prior functional study showing that the immunoregulatory protein RELMα and eosinophils contribute to female protection from high-fat diet-induced obesity, we used single-cell transcriptional profiling to study adipose eosinophil states at higher resolution. We identify six transcriptionally distinct eosinophil clusters whose relative abundance differs by sex, helminth infection, and RELMα status. Adipose tissue from females or helminth-infected mice is enriched for eosinophil clusters with type 2/homeostatic-associated transcriptional programs, whereas males and RELMα-deficient mice have increased representation of inflammatory/MHCII-associated clusters together with an altered predicted macrophage–eosinophil communication networks. Spectral flow cytometry and adipose tissue in situ hybridization independently support eosinophil heterogeneity and candidate chemokine-receptor interactions. Through single-cell regulatory network inference and clustering (SCENIC) analysis, we further identified transcription factor regulons unique to the specific eosinophil clusters, including sex-differential and high-fat diet enriched regulatory programs supported by target-gene expression patterns. Collectively, these data provide a framework for describing adipose eosinophil heterogeneity within a previously established RELMα–macrophage–eosinophil axis and identify candidate transcriptional and communication programs for future functional testing.
Related
- Eosinophils in autoimmune diseases: context-dependent pathogenesis, functional heterogeneity, and therapeutic translation
- Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice
- Lipolysis-driven communication between adipose tissue and liver: a key axis in metabolic regulation
- Breakdown of adipocyte-endothelial communication as a driver of adipose tissue dysfunction in obesity
- Human Subcutaneous Adipose Transcriptomes Link Mitochondrial Transcription to Metabolic Heterogeneity in Obesity.
BibTeX
@article{ruggieroruff2026singlecell,
title = {{Single-cell heterogeneity of adipose eosinophils is shaped by sex and RELMα and linked to macrophage communication networks in obesity}},
author = {Rebecca E Ruggiero-Ruff and Xinru Qiu and Lauren Vance and Yuxin He and Djurdjica Coss and Adam Godzik and Meera G Nair},
journal = {PNAS Nexus},
year = {2026},
month = oct,
doi = {10.1093/pnasnexus/pgag365},
url = {https://academic.oup.com/pnasnexus/advance-article/doi/10.1093/pnasnexus/pgag365/8995448},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-cell heterogeneity of adipose eosinophils is shaped by sex and RELMα and linked to macrophage communication networks in obesity
AU - Rebecca E Ruggiero-Ruff
AU - Xinru Qiu
AU - Lauren Vance
AU - Yuxin He
AU - Djurdjica Coss
AU - Adam Godzik
AU - Meera G Nair
PY - 2026
DA - 2026/10/24
JO - PNAS Nexus
DO - 10.1093/pnasnexus/pgag365
UR - https://academic.oup.com/pnasnexus/advance-article/doi/10.1093/pnasnexus/pgag365/8995448
AB - Eosinophils are immune cells with terminal effector functions in type 2 immune responses, yet recent findings suggest that they exhibit functional plasticity and heterogeneity dependent on tissue-specific cues. Building on our prior functional study showing that the immunoregulatory protein RELMα and eosinophils contribute to female protection from high-fat diet-induced obesity, we used single-cell transcriptional profiling to study adipose eosinophil states at higher resolution. We identify six transcriptionally distinct eosinophil clusters whose relative abundance differs by sex, helminth infection, and RELMα status. Adipose tissue from females or helminth-infected mice is enriched for eosinophil clusters with type 2/homeostatic-associated transcriptional programs, whereas males and RELMα-deficient mice have increased representation of inflammatory/MHCII-associated clusters together with an altered predicted macrophage–eosinophil communication networks. Spectral flow cytometry and adipose tissue in situ hybridization independently support eosinophil heterogeneity and candidate chemokine-receptor interactions. Through single-cell regulatory network inference and clustering (SCENIC) analysis, we further identified transcription factor regulons unique to the specific eosinophil clusters, including sex-differential and high-fat diet enriched regulatory programs supported by target-gene expression patterns. Collectively, these data provide a framework for describing adipose eosinophil heterogeneity within a previously established RELMα–macrophage–eosinophil axis and identify candidate transcriptional and communication programs for future functional testing.
SN - 2752-6542
ER -