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Eosinophils and Their Role in Allergy and Related Diseases
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Eosinophils and Their Role in Allergy and Related Diseases

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 14354

Special Issue Editor

Prof. Dr. Paige Lacy

E-Mail Website
Guest Editor
559 HMRC, Alberta Respiratory Centre, Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada
Interests: allergy; immunology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Eosinophils are enigmatic cells whose functional role within the immune system is still under intense scrutiny, and this has led to a greater appreciation of the contribution of eosinophils to allergy and related diseases. Understanding their function in these diseases has become especially pertinent since the introduction of highly successful anti-eosinophil biologic therapies to treat eosinophil-associated allergic diseases. In this Special Issue, we extend our understanding of the role of eosinophils in allergy, asthma, and related diseases. How eosinophils become elevated and activated, and the factors required for their proliferation and release of inflammatory mediators in allergies, are topics of interest in this collection of articles. I therefore welcome review and original research articles that are focused on the role of eosinophils in this domain. These articles should describe the function of eosinophils in allergic inflammation and how these may be modified by therapies such as anti-eosinophil biologics. Articles should also focus on feasible drug targets to regulate the number and activity of eosinophils in allergic diseases.

Prof. Dr. Paige Lacy
Guest Editor

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Keywords

  • eosinophils
  • asthma
  • allergy
  • inflammation
  • anti-eosinophil biologics
  • interleukin-5
  • interleukin-5 receptor
  • degranulation
  • mediator release

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Published Papers (7 papers)

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Research

Jump to: Review

17 pages, 3305 KB  
Article
Evolution of Blood Innate Immune Cell Phenotypes Following SARS-CoV-2 Infection in Hospitalized Patients with COVID-19
by Arnaud Dendooven, Stephane Esnault, Marie Jacob, Jacques Trauet, Emeline Delaunay, Thomas Guerrier, Amali E. Samarasinghe, Floriane Mirgot, Fanny Vuotto, Karine Faure, Julien Poissy, Marc Lambert, Myriam Labalette, Guillaume Lefèvre and Julie Demaret
Cells 2025, 14(14), 1093; https://doi.org/10.3390/cells14141093 - 17 Jul 2025
Cited by 1 | Viewed by 1736
Abstract
Innate immune cells appear to have an important implication in the resolution and/or the aggravation of the COVID-19 pathogenesis after infection with SARS-CoV-2. To better appreciate the role of these cells during COVID-19, changes in blood eosinophil, the neutrophil and monocyte count, and [...] Read more.
Innate immune cells appear to have an important implication in the resolution and/or the aggravation of the COVID-19 pathogenesis after infection with SARS-CoV-2. To better appreciate the role of these cells during COVID-19, changes in blood eosinophil, the neutrophil and monocyte count, and levels of surface protein markers have been reported. However, analyses at several timepoints of multiple surface markers on granulocytes and monocytes over a period of one month after a SARS-CoV-2 infection are missing. Therefore, in this study, we performed blood eosinophil, neutrophil, and monocyte phenotyping using a list of surface proteins and flow cytometry during a period of 30 days after the hospitalization of patients with severe SARS-CoV-2 infections. Blood cell counts were reported at seven different timepoints over the 30-day period as well as measures of multiple mediators in serum using a targeted multiplex assay approach. Our results indicate a 95% drop in the blood eosinophil count by D1, with eosinophils displaying a phenotype defined as CD69/CD63/CD125high and CCR3/CD44low during the early phases of hospitalization. Conversely, by D7 the neutrophil count increased significantly and displayed an immature, activated, and immunosuppressive phenotype (i.e., 3% of CD10/CD16low and CD10lowCD177high, 6.7% of CD11bhighCD62Llow, and 1.6% of CD16highCD62Llow), corroborated by enhanced serum proteins that are markers of neutrophil activation. Finally, our results suggest a rapid recruitment of non-classical monocytes leaving CD163/CD64high and CD32low monocytes in circulation during the very early phase. In conclusion, our study reveals potential very early roles for eosinophils and monocytes in the pathogenesis of COVID-19 with a likely reprogramming of eosinophils in the bone marrow. The exact roles of the pro-inflammatory neutrophils and the functions of the eosinophils and the monocytes, as well as these innate immune cell types, interplays need to be further investigated. Full article
(This article belongs to the Special Issue Eosinophils and Their Role in Allergy and Related Diseases)
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13 pages, 1406 KB  
Article
Humanized FcεRI Expressed on Mouse Eosinophils Mediates IgE-Facilitated Eosinophil Antigen Presentation
by Haibin Wang, Jean-Pierre Kinet and Peter F. Weller
Cells 2025, 14(4), 301; https://doi.org/10.3390/cells14040301 - 18 Feb 2025
Cited by 1 | Viewed by 2278
Abstract
High-affinity IgE receptors (FcεRI) are expressed on human blood eosinophils and may be upregulated on eosinophils at sites of allergic inflammation including atopic dermatitis and allergic asthma. FcεRI engagement, however, fails to elicit “effector” responses from eosinophils. Thus, a functional role for FcεRI [...] Read more.
High-affinity IgE receptors (FcεRI) are expressed on human blood eosinophils and may be upregulated on eosinophils at sites of allergic inflammation including atopic dermatitis and allergic asthma. FcεRI engagement, however, fails to elicit “effector” responses from eosinophils. Thus, a functional role for FcεRI on eosinophils has been uncertain. We evaluated the role of FcεRI in enhancing eosinophil antigen presentation in vivo by using humanized FcεRI α chain (hFcεRIα) transgenic mice. Eosinophils from hFcεRIα transgenic mice expressed humanized FcεRIα, with higher levels of eosinophils from the bronchoalveolar lavage of experimental asthma than those from polymyxin-elicited peritoneal lavage. The hFcεRIα-bearing eosinophils instilled intratracheally (i.t.) into recipient wild-type mice migrated from airways into paratracheal lymph nodes (pLNs) and spleens. Eosinophils, pretreated in vitro with nitrophenyl-ovalbumin ((NP)-OVA) and anti-NP human IgE complexes and instilled i.t., presented NP antigen via hFcεRIα to T cells more effectively than those pretreated with NP-OVA only, as assessed by pLN cell proliferation. IgE/FcεRIα-facilitated eosinophil antigen presentation resulted in increased IL-4 but not INF-γ production by pLN cells, with a bias towards Th2 cytokine production. Furthermore, cross-linking hFcεRIα on eosinophils increased eosinophil expressions of T cell costimulatory proteins CD40, CD80, and CD86. Humanized FcεRIα on murine eosinophils functions to enhance eosinophil antigen presentation capacities by mediating IgE-facilitated antigen presentation and upregulating expression of requisite T cell costimulatory proteins. Thus, a functional, non-“effector” role for FcεRI on eosinophils is revealed through identifying a means by which IgE may act on eosinophils to mediate their immunomodulatory, enhanced antigen presentation capabilities. Full article
(This article belongs to the Special Issue Eosinophils and Their Role in Allergy and Related Diseases)
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Graphical abstract

11 pages, 3447 KB  
Communication
CCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway Inflammation
by Yoshiki Kobayashi, Chu Hong Hanh, Naoto Yagi, Nhi Kieu Thi Le, Yasutaka Yun, Akihiro Shimamura, Kenta Fukui, Akitoshi Mitani, Kensuke Suzuki, Akira Kanda and Hiroshi Iwai
Cells 2025, 14(1), 33; https://doi.org/10.3390/cells14010033 - 31 Dec 2024
Cited by 3 | Viewed by 1763
Abstract
Eosinophilic chronic rhinosinusitis (ECRS), a CRS with nasal polyps (CRSwNP), is characterized by eosinophilic infiltration with type 2 inflammation and is highly associated with bronchial asthma. Intractable ECRS with poorly controlled asthma is recognized as a difficult-to-treat eosinophilic airway inflammation. Although eosinophils are [...] Read more.
Eosinophilic chronic rhinosinusitis (ECRS), a CRS with nasal polyps (CRSwNP), is characterized by eosinophilic infiltration with type 2 inflammation and is highly associated with bronchial asthma. Intractable ECRS with poorly controlled asthma is recognized as a difficult-to-treat eosinophilic airway inflammation. Although eosinophils are activated and coincubation with airway epithelial cells prolongs their survival, the interaction mechanism between eosinophils and epithelial cells is unclear. This study examined the effect of eosinophils on mucin glycoprotein 1 (MUC1), a member of membrane-bound mucin, in the airway epithelial cells, to elucidate the mechanisms of the eosinophil–airway epithelial cell interaction. Nasal polyp samples from patients with CRSwNP and BEAS-2B airway epithelial cells, coincubated with purified eosinophils, were stained with two MUC1 antibodies. To confirm the involvement of CCL4, an anti-CCL4 neutralizing antibody or recombinant CCL4 was used as needed. The immunofluorescence results revealed a negative correlation between the expression of full-length MUC1 and eosinophil count in nasal polyps. In BEAS-2B coincubated with eosinophils, full-length MUC1, but not the C-terminal domain, was reduced, and eosinophil survival was prolonged, which was concomitant with CCL4 increase, whereas the anti-CCL4 neutralizing antibody decreased these reactions. The survival of eosinophils that contacted recombinant MUC1 without the N-terminal domain was prolonged, and recombinant CCL4 increased the expression of metalloproteases. Increased CCL4 induces the contact between eosinophils and airway epithelial cells by shedding the MUC1 N-terminal domain and enhances eosinophil survival in eosinophilic airway inflammation. This novel mechanism may be a therapeutic target for difficult-to-treat eosinophilic airway inflammation. Full article
(This article belongs to the Special Issue Eosinophils and Their Role in Allergy and Related Diseases)
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23 pages, 3349 KB  
Article
Evidence for a Role of the Long Non-Coding RNA ITGB2-AS1 in Eosinophil Differentiation and Functions
by Timothée Fettrelet, Aref Hosseini, Jacqueline Wyss, Joanna Boros-Majewska, Darko Stojkov, Shida Yousefi and Hans-Uwe Simon
Cells 2024, 13(23), 1936; https://doi.org/10.3390/cells13231936 - 22 Nov 2024
Cited by 3 | Viewed by 2513
Abstract
Eosinophils, a type of granulocyte derived from myeloid precursors in the bone marrow, are distinguished by their cytoplasmic granules. They play crucial roles in immunoregulation, tissue homeostasis, and host defense, while also contributing to the pathogenesis of various inflammatory diseases. Although long non-coding [...] Read more.
Eosinophils, a type of granulocyte derived from myeloid precursors in the bone marrow, are distinguished by their cytoplasmic granules. They play crucial roles in immunoregulation, tissue homeostasis, and host defense, while also contributing to the pathogenesis of various inflammatory diseases. Although long non-coding RNAs (lncRNAs) are known to be involved in eosinophilic conditions, their specific expression and functions within eosinophils have not been thoroughly investigated, largely due to the reliance on tissue homogenates. In an effort to address this gap, we analyzed publicly available high-throughput RNA sequencing data to identify lncRNAs associated with eosinophilic conditions. Among the identified lncRNAs, ITGB2 antisense RNA 1 (ITGB2-AS1) was significantly downregulated in blood eosinophils from patients with hypereosinophilia. To further explore its role in eosinophil biology, we generated a stable ITGB2-AS1 knockdown in the HL-60 cell line. Interestingly, ITGB2-AS1 deficiency led to impaired eosinophil differentiation, as evidenced by a reduction in cytoplasmic granules and decreased expression of key eosinophil granule proteins, including eosinophil peroxidase (EPX) and major basic protein-1 (MBP-1). Additionally, ITGB2-AS1-deficient cells exhibited compromised eosinophil effector functions, with reduced degranulation and impaired production of reactive oxygen species (ROS). These findings suggest that ITGB2-AS1 plays a pivotal role in eosinophil differentiation and function, positioning it as a novel regulator in eosinophil biology. Full article
(This article belongs to the Special Issue Eosinophils and Their Role in Allergy and Related Diseases)
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Review

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22 pages, 816 KB  
Review
Understanding Eosinophil Heterogeneity: The Known and Unknown
by Alexander Ruzic, Michael Trus, Roma Sehmi and Manali Mukherjee
Cells 2026, 15(6), 564; https://doi.org/10.3390/cells15060564 - 21 Mar 2026
Viewed by 853
Abstract
Eosinophils are multifunctional granulocytes with central roles in the pathobiology of chronic airway diseases. While systemic eosinophilia (>300 cells/μL) is a well-established biomarker to guide therapeutic decision-making, accumulating evidence indicates that eosinophils are not a uniform population but instead exhibit substantial phenotypic and [...] Read more.
Eosinophils are multifunctional granulocytes with central roles in the pathobiology of chronic airway diseases. While systemic eosinophilia (>300 cells/μL) is a well-established biomarker to guide therapeutic decision-making, accumulating evidence indicates that eosinophils are not a uniform population but instead exhibit substantial phenotypic and functional heterogeneity across biological compartments, inflammatory states, and disease contexts. In this review, we synthesize the current understanding of eosinophil heterogeneity in airway diseases and critically evaluate the strengths and limitations of surface marker-based approaches, with emphasis on CD62L/L-selectin-defined subpopulations. Although CD62L-based stratification has provided valuable insight into eosinophil activation and tissue localization, its limited specificity, inconsistent clinical associations, and reliance on murine models restrict its utility as a framework for eosinophil subtyping in humans. We highlight how transcriptomic and proteomic profiling has transformed the field by revealing that peripheral blood eosinophils are largely quiescent, whereas disease-relevant functional specialization is predominantly acquired within inflamed tissues in response to cues from the local microenvironment. These molecular studies support a model in which eosinophil heterogeneity represents a continuum of activation rather than discrete, fixed subsets. A refined, integrative approach to understanding eosinophil heterogeneity is critical for improving patient stratification, predicting therapeutic responsiveness, and optimizing precision medicine strategies in chronic airway diseases. Full article
(This article belongs to the Special Issue Eosinophils and Their Role in Allergy and Related Diseases)
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24 pages, 2412 KB  
Review
Innate Immune Pairing: Eosinophils as Hidden Architects of T Cell Immunity
by Kriti Gupta, Natalie A. Falta and Lisa A. Spencer
Cells 2025, 14(22), 1826; https://doi.org/10.3390/cells14221826 - 20 Nov 2025
Cited by 2 | Viewed by 1480
Abstract
Eosinophils, once primarily considered strictly end-stage effector cells in parasitic infections and allergic inflammation, are now emerging as vital immunoregulatory cells. This review focuses on eosinophil contributions to cell-mediated adaptive immunity by exploring the multifaceted interactions between eosinophils and T cells that underlie [...] Read more.
Eosinophils, once primarily considered strictly end-stage effector cells in parasitic infections and allergic inflammation, are now emerging as vital immunoregulatory cells. This review focuses on eosinophil contributions to cell-mediated adaptive immunity by exploring the multifaceted interactions between eosinophils and T cells that underlie their unique contributions to immune modulation in allergic diseases. We begin by reviewing key features of eosinophil immunobiology within the context of their relevance to the development, differentiation, and function of CD4+ and CD8+ T cells in homeostasis and immunity. Building on this framework, we review recent literature revealing new roles for eosinophils in homeostatic immunosuppression, adaptive immune initiation, and immunomodulation within the context of an active immune response. We further explore the significance of eosinophil functionality impacting the structure and function of primary and secondary lymphoid organs, including thymic involution and regeneration, on cell-mediated immunity. This review presents an evolving paradigm that positions eosinophils as essential players in shaping multiple layers of the immune landscape in allergic diseases and beyond. Full article
(This article belongs to the Special Issue Eosinophils and Their Role in Allergy and Related Diseases)
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14 pages, 1475 KB  
Review
Spatial Eosinophil Phenotypes as Immunopathogenic Determinants in Inflammatory Diseases
by Jonas S. Erjefält
Cells 2025, 14(11), 847; https://doi.org/10.3390/cells14110847 - 5 Jun 2025
Cited by 3 | Viewed by 2412
Abstract
Eosinophils are increasingly recognized as adaptable immune cells that exhibit diverse phenotypes and effector functions across different tissues and disease states. While they can induce pathology through degranulation and cytotoxic mediator release, eosinophils also fulfill regulatory and tissue repair roles. Advances in single-cell [...] Read more.
Eosinophils are increasingly recognized as adaptable immune cells that exhibit diverse phenotypes and effector functions across different tissues and disease states. While they can induce pathology through degranulation and cytotoxic mediator release, eosinophils also fulfill regulatory and tissue repair roles. Advances in single-cell and spatial technologies have begun to reveal how microenvironmental cues (including cytokines, chemokines, and cell–cell interactions) shape eosinophil behavior in health and disease. These insights are critical for understanding why certain patients respond variably to therapies targeting eosinophils and related type 2 pathways. By dissecting eosinophil heterogeneity in real human tissues, researchers may identify new biomarkers, refine endotyping approaches, and develop more precise therapeutic strategies. This review summarizes emerging concepts of eosinophil biology in inflammatory conditions, highlights the impact of spatial context on eosinophil functions, and discusses the future of advanced phenotyping in guiding personalized treatments. Full article
(This article belongs to the Special Issue Eosinophils and Their Role in Allergy and Related Diseases)
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