May 2026
Tissue Environment Shapes Eosinophil Lifespan and Diversity
Article: Temporal and spatial atlas of eosinophil specialization across tissues
Hu Y, Wu L, Qu S, et al.
Nature Immunology. 2026
Reviewed by Roopa Hebbandi Nanjundappa, Dalhousie University, Halifax, Canada
A recent study by Hu et al. present a comprehensive multi-omics atlas of eosinophils across murine tissues, providing new insight into how these cells adapt to different environments. By integrating single-cell RNA sequencing with proteomic approaches, including antibody-sequencing, InfinityFlow, CyTOF, and flow cytometry, along with in vivo fate mapping using the Ms4a3CreERT2-Rosa26tdTomato system, the authors show that tissue residency time is a key factor shaping eosinophil identity. Read more
Eosinophils display clear tissue-specific differences at both gene and protein levels. Eight distinct eosinophil states were identified across bone marrow, blood, lung, colon, adipose tissue, and small intestine. While core markers such as Siglecf, Il5ra, Ccr3, and Epx are conserved, each tissue imprints unique features. For example, small intestinal eosinophils express Cd274, Cd22, Ahr, Itgax, and Fcgr4, whereas colon and adipose eosinophils exhibit distinct inflammatory and metabolic signatures. These findings are supported at the protein level by markers such as PD-L1, CD11c, CD16.2, and CD45RB.
Pseudotime analysis revealed a developmental progression from bone marrow progenitors to circulating and tissue-resident eosinophils. Fate-mapping experiments showed that eosinophil lifespan varies across tissues, with short-lived cells in the lung, intermediate populations in the colon, and long-lived populations in the small intestine and adipose tissue. These long-lived cells express enhanced survival genes, including Bcl2 family members and Xiap, supporting their persistence and diversification.
Using markers such as Clec12a (CD371), Itgal (CD11a), Fcgr4 (CD16.2), and Cd22, the authors defined eosinophil stages as early (E-Eos), mature (M-Eos), and specialized tissue-resident cells (Sp-Eos). Sp-Eos are enriched in tissues, particularly in the small intestine, where CD22⁺ and CD16.2⁺ cells accumulate and represent long-lived populations.
The small intestine emerges as a key site of eosinophil diversity, with multiple functional subsets. These align with previously described CD22⁺ and α4β7⁺ populations (Wang et al. 2022; Li et al. 2023; Kutyavin et al. 2024), but do not fit the activated versus basal classification from IL-5 overexpression models (Gurtner et al. 2023). This difference likely reflects cytokine-driven effects in IL-5 models rather than normal physiology. Overall, eosinophil identity is shaped by tissue signals and duration of residency, providing a new framework for understanding their roles in health and disease.
While the study provides an extensive characterization of eosinophil heterogeneity, functional validation linking specific subsets to defined roles in tissue homeostasis or disease remains limited. In addition, the reliance on murine models highlights the need for validation in human systems to determine the translational relevance of these specialized eosinophil states.
Roopa Hebbandi Nanjundappa, MSc, PhD, is an AAI postdoctoral fellow at Dalhousie University. She earned her PhD in Immunology from the University of Calgary, where her research focused on understanding how a gut microbial molecular mimic of pancreatic beta-cell auto-antigen can protect the host from inflammatory bowel disease. Currently, she is investigating the roles of mast cells and eosinophils in Respiratory Syncytial Virus (RSV) infection under the mentorship of Dr. Jean Marshall.
About the Author
The new “About the Author” feature spotlights the first author of an outstanding paper, offering readers a unique early career or trainee perspective on the work. The article, "Temporal and spatial atlas of eosinophil specialization across tissues," was selected for review by the Early Career Committee, reflecting its scientific impact as well as its relevance to emerging researchers in the field.
Yanan Hu earned her Bachelor's degree in Biological Sciences from Sichuan University, China. She is currently a Ph.D. student in the laboratory of Dr. Svetoslav Chakarov at the Shanghai Institute of Immunology, which is part of the Department of Immunology and Microbiology at Shanghai Jiao Tong University School of Medicine. Founded in 1979 and affiliated with the medical school, the institute focuses on four major research areas: autoimmune diseases, intestinal diseases, infectious diseases, and cancer immunotherapy.
Tell us about yourself. What is your academic background, and what are you currently working on?
My name is Yanan Hu. I am currently a Ph.D. candidate in the laboratory of Dr. Svetoslav Chakarov at the Shanghai Institute of Immunology, Department of Immunology and Microbiology at Shanghai Jiao Tong University School of Medicine. My research focuses on eosinophil heterogeneity and their homeostatic regulatory functions. Previously, I worked on constructing a single-cell spatiotemporal atlas of eosinophils across multiple tissues. Building on that foundation, I am now investigating the mechanisms that induce long-term survival in eosinophils, and how subsets with distinct lifespans become functionally specialized.
Why eosinophils? What initially drew you to this area of research?
My broader scientific interest lies in understanding the factors that drive the specification of myeloid cells. Taking macrophages as an example, we know that the tissue microenvironment (often referred to as the resident niche) and the duration of tissue residence are both critical in shaping their identity and function. However, whether this framework also applies to other myeloid cell types remains largely unexplored. Eosinophils represent a particularly intriguing case. Due to certain technical challenges associated with their cell identity, single-cell transcriptomic data for eosinophils have long been scarce. At the same time, recent studies have revealed that eosinophils are far more than just effector cells in type 2 immune responses; they also play extensive roles in maintaining tissue homeostasis. These gaps and emerging insights prompted us to place eosinophils at the center of our research.
About this study. What is the main takeaway or key message from your work?
In this Nature Immunology study, we present three core advances.
First, we constructed the first cross-tissue single-cell transcriptomic and proteomic atlas of eosinophils, revealing pronounced heterogeneity across organs and providing a foundational resource for future functional dissection of individual subsets.
Second, using lineage‑tracing models, we carried out the first systematic measurement of eosinophil tissue residence times in multiple organs, uncovering that eosinophil populations in different tissues possess markedly distinct lifespans.
Third, we demonstrated that tissue residence time is a key driver of eosinophil identity and tissue adaptation, acting in concert with the local microenvironment to shape their specialization at the sub‑tissue level.
Together, this comprehensive map of transcriptional, proteomic, and lifespan diversity not only decodes the principles governing eosinophil heterogeneity but also establishes a powerful platform for identifying regulatory mechanisms and subset‑specific functions. Ultimately, these insights lay the groundwork for therapeutic strategies that precisely target distinct eosinophil populations.