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Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop...
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Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2022 and 2023”

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 14244

Special Issue Editors

Prof. Dr. Yoshiyuki Yamada

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Guest Editor
Department of Pediatrics, Tokai University School of Medicine, Isehara, Kanagawa, Japan
Interests: allergy; eosinophilic gastrointestinal disorders; hypereosinophilic syndromes; food allergies; asthma
Prof. Dr. Akira Kanda

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Guest Editor
Center of Laboratory Medicine, Kansai Medical University Hospital, Hirakata, Osaka, Japan
Interests: allergy; allergic rhinitis; asthma; eosinophils
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The focus of this Special Issue is the biology or roles of eosinophils in allergy and related diseases, such as asthma, atopic dermatitis, allergic rhinitis, eosinophilic gastrointestinal diseases (EGIDs), hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic chronic rhinosinusitis (ECRS).

Eosinophils play a critical role in the pathogenesis of type two inflammation through the expression of surface receptors, including cytokine and chemokine receptors, lipid mediator receptors, pattern recognition receptors, adhesion molecules, Fc receptors, and Toll-like receptors, while eosinophils have biological functions, including the maintenance of homeostasis, host defense against infections, immune regulation, and anti-inflammatory and antitumorigenic activities. In addition, eosinophil biology itself has still not been fully elucidated.

To understand the biological aspects of eosinophils and associated disease, our workshop, “Workshop on Eosinophils in Allergy and Related Diseases (WEA)”, has been held annually in Japan for more than 30 years. In the annual meeting of the WEA, we discuss subjects regarding eosinophils in allergy, including 1) cell production/differentiation, 2) migration/infiltration, 3) structure/surface receptors, 4) activation, 5) intracellular signal transduction, 6) mediator/cytokine production, 7) role in disease pathogenesis, and 8) case reports.

Here, we selected authors from “The Workshop on Eosinophils in Allergy and Related Diseases 2022 (WEA 2022)” and all WEAs held before to submit papers to this Special Issue of Biomolecules. The purpose of this Special Issue is to contribute to the development of research by promoting a better understanding of the biology and clinical implications of eosinophils.

Prof. Dr. Yoshiyuki Yamada
Prof. Dr. Akira Kanda
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • allergic inflammation
  • asthma
  • atopic dermatitis
  • allergic rhinitis
  • allergic conjunctivitis
  • chronic rhinosinusitis with nasal polyp (CRSwNP)
  • eosinophils
  • eosinophilic pneumonia
  • eosinophilic chronic rhinosinusitis (ECRS)
  • eosinophilic gastrointestinal diseases (EGIDs)
  • hypereosinophilic syndromes (HESs)
  • eosinophilic granulomatosis with polyangiitis (EGPA)

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Related Special Issues

Published Papers (6 papers)

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Research

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17 pages, 1752 KiB  
Article
Moderate-High Blood Eosinophilia Is Associated with Increased Hospitalization and Other Asthma Comorbidities
by Sara Naharro-González, Clara Lorente-Sorolla, José Manuel Rodrigo-Muñoz, Marcela Valverde-Monge, Erwin Javier Pinillos-Robles, Diana Betancor, Mar Fernández-Nieto, Diana Sánchez-Mellado, Marta Gil-Martínez, Jessica Mireya Santillán-Coello, José Miguel Villacampa-Aubá, Ignacio Mahillo-Fernandez, Antonio Herrero-González, Alejandro Perez-González, María Jesús Rodríguez-Nieto and Victoria del Pozo
Biomolecules 2024, 14(1), 126; https://doi.org/10.3390/biom14010126 - 18 Jan 2024
Viewed by 2442
Abstract
(1) Background: Eosinophilia has traditionally been linked to eosinophilic asthma, for which it is the gold-standard prognostic biomarker. However, the association between eosinophilia and the presence of other diseases and comorbidities is yet unclear. (2) Methods: For this retrospective study, we reviewed the [...] Read more.
(1) Background: Eosinophilia has traditionally been linked to eosinophilic asthma, for which it is the gold-standard prognostic biomarker. However, the association between eosinophilia and the presence of other diseases and comorbidities is yet unclear. (2) Methods: For this retrospective study, we reviewed the electronic medical records of 49,909 subjects with blood eosinophilia to gather data on the presence of asthma, COPD, sleep apnea, tuberculosis, dyslipidemia, hypertension, and other cardiovascular diseases and severe CRSwNP among these subjects. Demographic features including age, sex, and smoking habits were collected, as well as the number of hospitalizations and emergency department visits. T-tests, ANOVA, Fisher test, and logistic regression models were used. (3) Results: For all age groups studied, eosinophilia was significantly more prevalent among asthmatic subjects than nonasthmatics, especially in patients also presenting CRSwNP, hypertension, and dyslipidemia. The likelihood of developing asthma, COPD, and CRSwNP, and hospitalization, was increased when BEC was above 600 eosinophils/μL. The association between asthma, CRSwNP, and BEC was corroborated by multiple logistic regressions models. (4) Conclusions: We demonstrated the association of having over 600 blood eosinophils/μL with a higher number of hospitalizations and comorbidities (CRSwNP and COPD), which proves that BEC is a highly useful parameter to consider in subjects who present blood eosinophilia. Full article
(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2022 and 2023”)
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14 pages, 4228 KiB  
Article
Eosinophils Contribute to Oral Tolerance via Induction of RORγt-Positive Antigen-Presenting Cells and RORγt-Positive Regulatory T Cells
by Shunjiro Kurihara, Kotaro Suzuki, Masaya Yokota, Takashi Ito, Yuki Hayashi, Ryo Kikuchi, Takahiro Kageyama, Kazuyuki Meguro, Shigeru Tanaka, Arifumi Iwata, Yoshiyuki Goto, Akira Suto and Hiroshi Nakajima
Biomolecules 2024, 14(1), 89; https://doi.org/10.3390/biom14010089 - 10 Jan 2024
Cited by 1 | Viewed by 1865
Abstract
Oral tolerance has been defined as the specific suppression of immune responses to an antigen by prior oral administration of the antigen. It has been thought to serve to suppress food allergy. Previous studies have shown that dendritic cells (DCs) and regulatory T [...] Read more.
Oral tolerance has been defined as the specific suppression of immune responses to an antigen by prior oral administration of the antigen. It has been thought to serve to suppress food allergy. Previous studies have shown that dendritic cells (DCs) and regulatory T cells (Tregs) are involved in the induction of oral tolerance. However, the detailed mechanisms of Treg induction in oral tolerance remain largely unknown. Eosinophils have been recognized as effector cells in allergic diseases, but in recent years, the diverse functions of tissue-resident eosinophils have been reported. Eosinophils in the intestine have been reported to induce Tregs by releasing TGF-β, but the role of eosinophils in oral tolerance is still controversial. In this study, we analyzed the roles of eosinophils in oral tolerance using eosinophil-deficient ΔdblGATA mice (mice lacking a high-affinity GATA-binding site in the GATA1 promoter). ΔdblGATA mice showed impaired antigen-induced oral tolerance compared to wild-type mice. The induction of RORγt+ Tregs in mesenteric lymph nodes (MLNs) by oral tolerance induction was impaired in ΔdblGATA mice compared to wild-type mice. An increase in RORγt+ antigen-presenting cells (APCs), which are involved in RORγt+ Treg differentiation, in the intestine and MLNs was not seen in ΔdblGATA mice. Notably, the expansion of group 3 innate lymphoid cells (ILC3s), a subset of RORγt+ APCs, by oral tolerance induction was seen in wild-type mice but not ΔdblGATA mice. These results suggest that eosinophils are crucial in the induction of oral tolerance, possibly via the induction of RORγt+ APCs and RORγt+ Tregs. Full article
(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2022 and 2023”)
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18 pages, 1714 KiB  
Article
Pretreatment Frequency of Circulating Th17 Cells and FeNO Levels Predicted the Real-World Response after 1 Year of Benralizumab Treatment in Patients with Severe Asthma
by Yuuki Sandhu, Norihiro Harada, Hitoshi Sasano, Sonoko Harada, Shoko Ueda, Tomohito Takeshige, Yuki Tanabe, Ayako Ishimori, Kei Matsuno, Sumiko Abe, Tetsutaro Nagaoka, Jun Ito, Asako Chiba, Hisaya Akiba, Ryo Atsuta, Kenji Izuhara, Sachiko Miyake and Kazuhisa Takahashi
Biomolecules 2023, 13(3), 538; https://doi.org/10.3390/biom13030538 - 15 Mar 2023
Cited by 4 | Viewed by 2183
Abstract
Benralizumab treatment reduces exacerbations and improves symptom control and quality of life in patients with severe eosinophilic asthma. However, the determination of biomarkers that predict therapeutic effectiveness is required for precision medicine. Herein, we elucidated the dynamics of various parameters before and after [...] Read more.
Benralizumab treatment reduces exacerbations and improves symptom control and quality of life in patients with severe eosinophilic asthma. However, the determination of biomarkers that predict therapeutic effectiveness is required for precision medicine. Herein, we elucidated the dynamics of various parameters before and after treatment as well as patient characteristics predictive of clinical effectiveness after 1 year of benralizumab treatment in severe asthma in a real-world setting. Thirty-six patients with severe asthma were treated with benralizumab for 1 year. Lymphocyte subsets in peripheral blood samples were analyzed using flow cytometry. Treatment effectiveness was determined based on the ACT score, forced expiratory volume in 1 s (FEV1), and the number of exacerbations. Benralizumab provided symptomatic improvement in severe asthma. Benralizumab significantly decreased peripheral blood eosinophil and basophil counts and the frequencies of regulatory T cells (Tregs), and increased the frequencies of Th2 cells. To our knowledge, this is the first study to show benralizumab treatment increasing circulating Th2 cells and decreasing circulating Tregs. Finally, the ROC curve to discriminate patients who achieved clinical effectiveness of benralizumab treatment revealed that the frequency of circulating Th17 cells and FeNO levels might be used as parameters for predicting the real-world response of benralizumab treatment in patients with severe asthma. Full article
(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2022 and 2023”)
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Review

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15 pages, 769 KiB  
Review
The Possible Roles of IL-4/IL-13 in the Development of Eosinophil-Predominant Severe Asthma
by Kazuyuki Nakagome and Makoto Nagata
Biomolecules 2024, 14(5), 546; https://doi.org/10.3390/biom14050546 - 2 May 2024
Cited by 4 | Viewed by 2890
Abstract
Bronchial asthma is characterized by airway inflammation, airway hyperresponsiveness, and reversible airway obstruction. Eosinophils contribute to the pathogenesis of airway disease mainly by releasing eosinophil-specific granules, lipid mediators, superoxide anions, and their DNA. Type-2 cytokines such as interleukin (IL)-4 and IL-13 also play [...] Read more.
Bronchial asthma is characterized by airway inflammation, airway hyperresponsiveness, and reversible airway obstruction. Eosinophils contribute to the pathogenesis of airway disease mainly by releasing eosinophil-specific granules, lipid mediators, superoxide anions, and their DNA. Type-2 cytokines such as interleukin (IL)-4 and IL-13 also play roles in the development of bronchial asthma. Among these cytokines, IL-4 is involved in T-cell differentiation, B-cell activation, B-cell differentiation into plasma cells, and the production of immunoglobulin E. Although IL-13 has similar effects to IL-4, IL-13 mainly affects structural cells, such as epithelial cells, smooth muscle cells, and fibroblasts. IL-13 induces the differentiation of goblet cells that produce mucus and induces the airway remodeling, including smooth muscle hypertrophy. IL-4 and IL-13 do not directly activate the effector functions of eosinophils; however, they can induce eosinophilic airway inflammation by upregulating the expression of vascular cell adhesion molecule-1 (for adhesion) and CC chemokine receptor 3 ligands (for migration). Dupilumab, a human anti-IL-4 receptor α monoclonal antibody that inhibits IL-4 and IL-13 signaling, decreases asthma exacerbations and mucus plugs and increases lung function in moderate to severe asthma. In addition, dupilumab is effective for chronic rhinosinusitis with nasal polyps and for atopic dermatitis, and IL-4/IL-13 blocking is expected to suppress allergen sensitization, including transcutaneous sensitization and atopic march. Full article
(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2022 and 2023”)
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17 pages, 3099 KiB  
Review
Review of Non-Eosinophilic Esophagitis-Eosinophilic Gastrointestinal Disease (Non-EoE-EGID) and a Case Series of Twenty-Eight Affected Patients
by Yoshikazu Kinoshita and Tsuyoshi Sanuki
Biomolecules 2023, 13(9), 1417; https://doi.org/10.3390/biom13091417 - 20 Sep 2023
Cited by 3 | Viewed by 2007
Abstract
Eosinophilic gastrointestinal disease (EGID) is divided into eosinophilic esophagitis (EoE) and non-eosinophilic esophagitis eosinophilic gastrointestinal disease (non-EoE-EGID) based on the involved gastrointestinal segments. Reports regarding non-EoE-EGID are limited, in part because of its rarity. The present study was performed to review non-EoE-EGID, including [...] Read more.
Eosinophilic gastrointestinal disease (EGID) is divided into eosinophilic esophagitis (EoE) and non-eosinophilic esophagitis eosinophilic gastrointestinal disease (non-EoE-EGID) based on the involved gastrointestinal segments. Reports regarding non-EoE-EGID are limited, in part because of its rarity. The present study was performed to review non-EoE-EGID, including its pathogenesis, diagnosis, treatment, and prognosis. Additionally, details regarding 28 cases of non-EoE-EGID recently diagnosed at our Japanese tertial medical center are presented and compared with 20 EoE cases diagnosed during the same period at the same medical center. Comparisons of the two groups clarified differences regarding age- and gender-dependent prevalence between the two conditions, and also showed that systemic involvement and disease severity were greater in the non-EoE-EGID patients. Notably, diagnosis of non-EoE-EGID is difficult because of its lack of specific or characteristic symptoms and endoscopic findings. The clinical characteristics of EoE and non-EoE-EGID differ in many ways, while they also share several genetic, clinical, laboratory, and histopathological features. Full article
(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2022 and 2023”)
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Other

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10 pages, 5153 KiB  
Brief Report
CD69 Signaling in Eosinophils Induces IL-10 Production and Apoptosis via the Erk1/2 and JNK Pathways, Respectively
by Dan Van Bui, Linh Manh Nguyen, Akira Kanda, Hanh Hong Chu, Nhi Kieu Thi Le, Yasutaka Yun, Yoshiki Kobayashi, Kensuke Suzuki, Akitoshi Mitani, Akihiro Shimamura, Kenta Fukui, Shunsuke Sawada, David Dombrowicz and Hiroshi Iwai
Biomolecules 2024, 14(3), 360; https://doi.org/10.3390/biom14030360 - 18 Mar 2024
Viewed by 1637
Abstract
Introduction: Eosinophils contribute to the pathogenesis of allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. We previously reported that human tissue eosinophils have high CD69 expression compared to blood eosinophils, and its expression is correlated with disease severity and the number of [...] Read more.
Introduction: Eosinophils contribute to the pathogenesis of allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. We previously reported that human tissue eosinophils have high CD69 expression compared to blood eosinophils, and its expression is correlated with disease severity and the number of infiltrated eosinophils. However, biological CD69 signaling activity in eosinophils remains unclear. Methods: CD69 expression on lung tissue eosinophils obtained from mice with ovalbumin-induced asthma was measured using flow cytometry. CD69 crosslinking was performed on eosinophils purified from the spleen of IL-5 transgenic mice to investigate CD69 signaling and its function in eosinophils. Then, qPCR, Western blot, enzyme-linked immunosorbent assay, and survival assay results were analyzed. Results: Surface CD69 expression on lung tissue eosinophils in the asthma mice model was 2.91% ± 0.76%, whereas no expression was detected in the healthy group. CD69-expressed eosinophils intrinsically have an upregulation of IL-10 mRNA expression. Moreover, CD69 crosslinking induced further pronounced IL-10 production and apoptosis; these responses were mediated via the Erk1/2 and JNK pathways, respectively. Conclusions: Our results suggested that CD69+ eosinophils play an immunoregulator role in type 2 inflammation, whereas activated tissue eosinophils contribute to the pathogenesis of asthma. Full article
(This article belongs to the Special Issue Eosinophils in Allergy and Related Diseases—Selected Papers from “The Workshop on Eosinophils in Allergy and Related Diseases 2022 and 2023”)
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