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Cells
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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 September 2025 | Viewed by 3425

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 (3 papers)

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Research

13 pages, 1406 KiB  
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
Viewed by 614
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 KiB  
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
Viewed by 889
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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Figure 1

23 pages, 3349 KiB  
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
Viewed by 1376
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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