FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Allergy2025; 80(12); 3377-3390; doi: 10.1111/all.70020

Anti-IL-5 Vaccination Dampens Allergen-Specific IgE Levels and Modulates IL-4 and IL-5 Th2 Cytokines in Skin Allergy of Mice and Horses.

Abstract: Skin allergies are among the most frequent types of allergies, where continuous investigation of the pathological immune mechanisms is required for a better understanding and a more effective treatment of the disease. In this study, we aimed to investigate the effect of interleukin (IL)-5 vaccination on allergen-specific IgE antibodies as well as T cell cytokine modulation in skin allergy using a mouse model and a naturally occurring disease in horses. Methods: Ovalbumin (OVA)-sensitized mice, as well as horses affected by equine insect bite hypersensitivity (IBH) were administered an anti-IL-5 vaccination, and allergen-specific IgE and IgG were quantified in the blood. Additionally, mRNA and protein expression of T cell cytokines of in vitro allergen re-stimulated murine splenocytes and equine peripheral blood mononuclear cells (PBMCs), as well as in IBH lesional skin biopsies, were investigated using qPCR and ELISA. Clinical signs were recorded by ear swelling in mice. Results: Our data showed a significant decrease in allergen-specific immunoglobulins (Igs) in IL-5-vaccinated mice, as well as a reduction in allergen-specific IgE in horses. Furthermore, protein production of T cell cytokines IL-4 and IFNγ in mice, as well as mRNA expression of IL-4, IL-5, IL-13, and IFNγ in lesional skin of the horses, was significantly decreased upon vaccination when compared to the placebo group. Furthermore, we demonstrated that CD4 cells in IBH-affected horses are highly enriched with the GATA3 transcription factor, responsible for IL-5 mRNA production and differentiation of Th2 cells. Additionally, increased IL-4 mRNA expression in IBH horses was shown to be CD4MHC-IIcell dependent. Conclusions: IL-5 vaccination significantly decreased allergen-specific IgE in both the murine skin allergy model and horses with naturally occurring allergic skin disease, as well as alleviated clinical signs of the diseases. We suggest that the IL-5 depletion may modulate the IL-4 levels originating from non-T cell sources. This is the first study showing that an IL-5 vaccination leads to a decrease in allergen-specific IgE levels, potentially suggesting its use in prophylactic settings for high-risk patients.
© 2025 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
Get Full Text
Publication Date: 2025-08-21 PubMed ID: 40838325PubMed Central: PMC12666748DOI: 10.1111/all.70020Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study investigates how vaccination against interleukin-5 (IL-5) affects allergen-specific immune responses, particularly IgE antibody levels and T helper 2 (Th2) cytokines, in skin allergies using both mice and horses as model systems.
  • The findings reveal that anti-IL-5 vaccination reduces allergen-specific IgE levels and modulates Th2 cytokines, which may help alleviate allergic symptoms and suggest potential therapeutic benefits for allergic skin diseases.

Background and Objectives

  • Skin allergies are common and involve complex immune system reactions that are not fully understood.
  • Interleukin-5 (IL-5) is a cytokine involved in the promotion of eosinophils and Th2 immune responses, both key players in allergic inflammation.
  • The study aimed to explore the effect of an anti-IL-5 vaccine on:
    • Allergen-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibody levels.
    • The modulation of T cell cytokines related to Th2 immune responses, such as IL-4, IL-5, and IL-13, as well as interferon gamma (IFNγ) which is involved in Th1 responses.
    • Clinical allergy symptoms in both a controlled mouse model and naturally occurring equine insect bite hypersensitivity (IBH), a type of allergic skin disease in horses.

Methods

  • Animals and Treatments:
    • Mice were sensitized with ovalbumin (OVA) to induce a skin allergic response and subsequently vaccinated with an anti-IL-5 vaccine.
    • Horses affected by IBH, an allergic skin disease caused by insect bites, were also vaccinated with the anti-IL-5 formulation.
  • Immunological Assessments:
    • Measurement of allergen-specific IgE and IgG antibodies in the blood using serological tests.
    • Quantification of T cell cytokine expression at both mRNA and protein levels:
      • Murine splenocytes and equine peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with allergens to assess cytokine responses.
      • Lesional skin biopsies from horses were analyzed by qPCR and ELISA to determine local cytokine expression.
  • Clinical Evaluation:
    • In mice, allergen-induced ear swelling was recorded as a measure of allergic inflammation.

Key Results

  • Reduction in Allergen-Specific Antibodies:
    • IL-5 vaccination led to a significant decrease in allergen-specific IgE and IgG in mice.
    • Significant reduction in allergen-specific IgE was also observed in IBH-affected horses after vaccination.
  • Altered Cytokine Profiles:
    • Mice showed decreased protein levels of IL-4 and IFNγ following vaccination.
    • In horses, mRNA levels of IL-4, IL-5, IL-13, and IFNγ in lesional skin were significantly decreased in vaccinated animals compared to placebo controls.
  • Immunological Insights:
    • CD4+ T cells in horses with IBH were found to be enriched in the transcription factor GATA3, which promotes IL-5 production and Th2 cell differentiation.
    • IL-4 expression in IBH horses appeared to depend on interactions between CD4+ T cells and MHC-II expressing cells, suggesting an immune cell collaboration in cytokine production.
  • Clinical Improvement:
    • Mice vaccinated with anti-IL-5 exhibited alleviation of allergic clinical signs such as ear swelling.

Conclusions and Implications

  • Anti-IL-5 vaccination successfully decreased allergen-specific IgE levels and modulated Th2 cytokine responses associated with allergic skin diseases.
  • The modulation of IL-4—possibly originating from non-T cell sources due to IL-5 depletion—suggests a broader immunoregulatory effect of the vaccination.
  • This study provides the first evidence that targeting IL-5 via vaccination can reduce allergen-specific IgE, which is a key factor in allergic reactions.
  • The findings indicate potential use of IL-5 vaccination as a prophylactic or therapeutic approach in animals and potentially humans at high risk of skin allergies.
  • Further research may explore the role of IL-5 vaccines in other allergic diseases and the underlying mechanisms of immune modulation.

Cite This Article

APA
Jebbawi F, Olomski F, Inversini V, Keller G, Rhiner T, Waldern N, Lam J, Pantelyushin S, Canonica F, Birkmann K, Johansen P, Kündig TM, Fettelschoss-Gabriel A. (2025). Anti-IL-5 Vaccination Dampens Allergen-Specific IgE Levels and Modulates IL-4 and IL-5 Th2 Cytokines in Skin Allergy of Mice and Horses. Allergy, 80(12), 3377-3390. https://doi.org/10.1111/all.70020

Publication

Allergy
ISSN: 1398-9995
NlmUniqueID: 7804028
Country: Denmark
Language: English
Volume: 80
Issue: 12
Pages: 3377-3390

Researcher Affiliations

Jebbawi, Fadi
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zürich, Switzerland.
  • Evax AG, Guntershausen, Switzerland.
Olomski, Florian
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zürich, Switzerland.
  • Evax AG, Guntershausen, Switzerland.
Inversini, Victoria
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zürich, Switzerland.
  • Evax AG, Guntershausen, Switzerland.
Keller, Giulia
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zürich, Switzerland.
  • Evax AG, Guntershausen, Switzerland.
Rhiner, Tanya
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Evax AG, Guntershausen, Switzerland.
Waldern, Nina
  • Evax AG, Guntershausen, Switzerland.
Lam, Juwela
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zürich, Switzerland.
  • Evax AG, Guntershausen, Switzerland.
Pantelyushin, Stanislav
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zürich, Switzerland.
  • Evax AG, Guntershausen, Switzerland.
Canonica, Fabia
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zürich, Switzerland.
  • Evax AG, Guntershausen, Switzerland.
Birkmann, Katharina
  • Evax AG, Guntershausen, Switzerland.
  • Equine Department, Veterinary Faculty, Ludwig Maximilians University Munich LMU, Oberschleißheim, Germany.
Johansen, Pål
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zürich, Switzerland.
Kündig, Thomas M
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zürich, Switzerland.
Fettelschoss-Gabriel, Antonia
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zürich, Switzerland.
  • Evax AG, Guntershausen, Switzerland.

MeSH Terms

  • Animals
  • Horses
  • Immunoglobulin E / immunology
  • Immunoglobulin E / blood
  • Mice
  • Interleukin-5 / immunology
  • Interleukin-5 / antagonists & inhibitors
  • Allergens / immunology
  • Interleukin-4 / metabolism
  • Interleukin-4 / immunology
  • Cytokines / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Vaccination
  • Disease Models, Animal
  • Female
  • Horse Diseases / immunology
  • Dermatitis, Atopic / immunology
  • Hypersensitivity / immunology
  • Insect Bites and Stings / immunology

Grant Funding

  • EVAX AG (CH)
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • Kommission für Technologie und Innovation (KTI)

Conflict of Interest Statement

F.J., V.I., G.K., T.R., N.W., J.L., F.C., K.B., T.M.K., and A.F.‐G. are involved in the development of therapeutic equine vaccines. F.O., S.P., and P.J. have no financial or personal conflicts of interest.

References

This article includes 89 references
  1. Mitson‐Salazar A, Prussin C. Pathogenic Effector Th2 Cells in Allergic Eosinophilic Inflammatory Disease. Frontiers in Medicine 4 (2017): 165.
    pmc: PMC5635264pubmed: 29057225
  2. Prussin C. Cytokine Flow Cytometry: Understanding Cytokine Biology at the Single‐Cell Level. Journal of Clinical Immunology 17, no. 3 (1997): 195–204.
    pubmed: 9168399
  3. Prussin C, Lee J, Foster B. Eosinophilic Gastrointestinal Disease and Peanut Allergy Are Alternatively Associated With IL‐5+ and IL‐5(−) T(H)2 Responses. Journal of Allergy and Clinical Immunology 124, no. 6 (2009): 1326–1332.e6.
    pmc: PMC2994258pubmed: 20004787
  4. Wagner B. IgE in Horses: Occurrence in Health and Disease. Veterinary Immunology and Immunopathology 132, no. 1 (2009): 21–30.
    pubmed: 19819562
  5. Schaffartzik A, Hamza E, Janda J, Crameri R, Marti E, Rhyner C. Equine Insect Bite Hypersensitivity: What Do We Know?. Veterinary Immunology and Immunopathology 147, no. 3–4 (2012): 113–126.
    pubmed: 22575371
  6. Woodfolk J A. T‐Cell Responses to Allergens. Journal of Allergy and Clinical Immunology 119, no. 2 (2007): 280–294; quiz 95‐6.
    pubmed: 17291848
  7. Blanchard C, Rothenberg M E. Basic Pathogenesis of Eosinophilic Esophagitis. Gastrointestinal Endoscopy Clinics of North America 18, no. 1 (2008): 133–143. x.
    pmc: PMC2194642pubmed: 18061107
  8. Strath M, Dent L, Sanderson C. Infection of IL5 Transgenic Mice With Mesocestoides Corti Induces Very High Levels of IL5 but Depressed Production of Eosinophils. Experimental Hematology 20, no. 2 (1992): 229–234.
    pubmed: 1544392
  9. Kopf M, Brombacher F, Hodgkin P D. IL‐5‐Deficient Mice Have a Developmental Defect in CD5+ B‐1 Cells and Lack Eosinophilia but Have Normal Antibody and Cytotoxic T Cell Responses. Immunity 4, no. 1 (1996): 15–24.
    pubmed: 8574848
  10. Collins P D, Marleau S, Griffiths‐Johnson D A, Jose P J, Williams T J. Cooperation Between Interleukin‐5 and the Chemokine Eotaxin to Induce Eosinophil Accumulation In Vivo. Journal of Experimental Medicine 182, no. 4 (1995): 1169–1174.
    pmc: PMC2192289pubmed: 7561691
  11. Robinson D S. Mepolizumab for Severe Eosinophilic Asthma. Expert Review of Respiratory Medicine 7, no. 1 (2013): 13–17.
    pubmed: 23362812
  12. Leon‐Ferre R A, Weiler C R, Halfdanarson T R. Hypereosinophilic Syndrome Presenting as an Unusual Triad of Eosinophilia, Severe Thrombocytopenia, and Diffuse Arterial Thromboses, With Good Response to Mepolizumab. Clinical Advances in Hematology & Oncology 11, no. 5 (2013): 317–319.
    pubmed: 23880717
  13. Ortega H G, Yancey S W, Mayer B. Severe Eosinophilic Asthma Treated With Mepolizumab Stratified by Baseline Eosinophil Thresholds: A Secondary Analysis of the DREAM and MENSA Studies. Lancet Respiratory Medicine 4, no. 7 (2016): 549–556.
    pubmed: 27177493
  14. Perez de Llano L A, Dacal Rivas D, Cosio B G. Mepolizumab and Reslizumab, Two Different Options for Severe Asthma Patients With Prior Failure to Omalizumab. Allergy 75, no. 4 (2020): 940–942.
    pubmed: 31483864
  15. Wechsler M E, Hickey L, Garin M, Chauhan A. Efficacy of Reslizumab Treatment in Exacerbation‐Prone Patients With Severe Eosinophilic Asthma. Journal of Allergy and Clinical Immunology: In Practice 8, no. 10 (2020): 3434–3442.e4.
    pubmed: 32562877
  16. Gauvreau GM, Sehmi R, FitzGerald JM. Benralizumab for Allergic Asthma: A Randomised, Double‐Blind, Placebo‐Controlled, Trial. European Respiratory Journal 64 (2024): 2400512.
    pmc: PMC11391094pubmed: 39060015
  17. Pini L, Bagnasco D, Beghe B. Unlocking the Long‐Term Effectiveness of Benralizumab in Severe Eosinophilic Asthma: A Three‐Year Real‐Life Study. Journal of Clinical Medicine 13, no. 10 (2024): 3013.
    pmc: PMC11122375pubmed: 38792553
  18. Rothenberg ME, Dellon ES, Collins MH. Eosinophil Depletion With Benralizumab for Eosinophilic Esophagitis. New England Journal of Medicine 390, no. 24 (2024): 2252–2263.
    pubmed: 38924732
  19. Fettelschoss‐Gabriel A, Fettelschoss V, Thoms F. Treating Insect‐Bite Hypersensitivity in Horses With Active Vaccination Against IL‐5. Journal of Allergy and Clinical Immunology 142, no. 4 (2018): 1194–1205.e3.
    pubmed: 29627082
  20. Fettelschoss‐Gabriel A, Fettelschoss V, Olomski F. Active Vaccination Against Interleukin‐5 as Long‐Term Treatment for Insect‐Bite Hypersensitivity in Horses. Allergy 74, no. 3 (2019): 572–582.
    pmc: PMC6587569pubmed: 30402930
  21. Schwarz EJF, Keller G, Rhiner T. Phenotypic Shift of an Inflammatory Eosinophil Subset Into a Steady‐State Resident Phenotype After 2 Years of Vaccination Against IL‐5 in Equine Insect Bite Hypersensitivity. Veterinary Sciences 11 (2024): 476.
    pmc: PMC11512288pubmed: 39453068
  22. Rhiner T, Fettelschoss V, Schoster A, Birkmann K, Fettelschoss‐Gabriel A. Targeting Eosinophils by Active Vaccination Against Interleukin‐5 Reduces Basophil Counts in Horses With Insect Bite Hypersensitivity in the 2nd Year of Vaccination. Veterinary Journal 288 (2022): 105896.
    pubmed: 36126798
  23. Jonsdottir S, Fettelschoss V, Olomski F. Safety Profile of a Virus‐Like Particle‐Based Vaccine Targeting Self‐Protein Interleukin‐5 in Horses. Vaccine 8, no. 2 (2020): 213.
    pmc: PMC7349629pubmed: 32397549
  24. Zou Y, Sonderegger I, Lipowsky G. Combined Vaccination Against IL‐5 and Eotaxin Blocks Eosinophilia in Mice. Vaccine 28, no. 18 (2010): 3192–3200.
    pubmed: 20189490
  25. Li M, Hener P, Zhang Z, Kato S, Metzger D, Chambon P. Topical Vitamin D3 and Low‐Calcemic Analogs Induce Thymic Stromal Lymphopoietin in Mouse Keratinocytes and Trigger an Atopic Dermatitis. Proceedings of the National Academy of Sciences of the United States of America 103, no. 31 (2006): 11736–11741.
    pmc: PMC1544239pubmed: 16880407
  26. Li M, Hener P, Zhang Z, Ganti KP, Metzger D, Chambon P. Induction of Thymic Stromal Lymphopoietin Expression in Keratinocytes Is Necessary for Generating an Atopic Dermatitis Upon Application of the Active Vitamin D3 Analogue MC903 on Mouse Skin. Journal of Investigative Dermatology 129, no. 2 (2009): 498–502.
    pubmed: 18650845
  27. Schmitz N, Dietmeier K, Bauer M. Displaying Fel d1 on Virus‐Like Particles Prevents Reactogenicity Despite Greatly Enhanced Immunogenicity: A Novel Therapy for Cat Allergy. Journal of Experimental Medicine 206, no. 9 (2009): 1941–1955.
    pmc: PMC2737174pubmed: 19667059
  28. Leuthard DS, Duda A, Freiberger SN. Microcrystalline Tyrosine and Aluminum as Adjuvants in Allergen‐Specific Immunotherapy Protect From IgE‐Mediated Reactivity in Mouse Models and Act Independently of Inflammasome and TLR Signaling. Journal of Immunology 200, no. 9 (2018): 3151–3159.
    pmc: PMC5911931pubmed: 29592962
  29. Schaffartzik A, Marti E, Torsteinsdottir S, Mellor PS, Crameri R, Rhyner C. Selective Cloning, Characterization, and Production of the Culicoides Nubeculosus Salivary Gland Allergen Repertoire Associated With Equine Insect Bite Hypersensitivity. Veterinary Immunology and Immunopathology 139, no. 2–4 (2011): 200–209.
    pubmed: 21071100
  30. Jonsdottir S, Torsteinsdottir S, Svansson V. Comparison of Recombinant Culicoides Allergens Produced in Different Expression Systems for IgE Serology of Insect Bite Hypersensitivity in Horses of Different Origins. Veterinary Immunology and Immunopathology 238 (2021): 110289.
    pubmed: 34214910
  31. Peeters LM, Janssens S, Schaffartzik A, Marti E, Buys N. Evaluation of IgE Levels Against Culicoides Nubeculosus Allergens in Belgian Warmblood Horses. Communications in Agricultural and Applied Biological Sciences 77, no. 1 (2012): 218–222.
    pubmed: 22558784
  32. van der Meide NM, Savelkoul HF, Meulenbroeks C, Ducro BJ, Tijhaar E. Evaluation of a Diagnostic ELISA for Insect Bite Hypersensitivity in Horses Using Recombinant Obsoletus Complex Allergens. Veterinary Journal 200, no. 1 (2014): 31–37.
    pubmed: 24703873
  33. Cahenzli J, Koller Y, Wyss M, Geuking MB, McCoy KD. Intestinal Microbial Diversity During Early‐Life Colonization Shapes Long‐Term IgE Levels. Cell Host & Microbe 14, no. 5 (2013): 559–570.
    pmc: PMC4049278pubmed: 24237701
  34. Jonsdottir S, Hamza E, Janda J. Developing a Preventive Immunization Approach Against Insect Bite Hypersensitivity Using Recombinant Allergens: A Pilot Study. Veterinary Immunology and Immunopathology 166, no. 1–2 (2015): 8–21.
    pubmed: 26004943
  35. Pantelyushin S, Rhiner T, Jebbawi F. Interleukin 5‐Dependent Inflammatory Eosinophil Subtype Involved in Allergic Insect Bite Hypersensitivity of Horses. Allergy 78, no. 11 (2023): 3020–3023.
    pubmed: 37605865
  36. Nunomura S, Ito R, Nanri Y. Novel Mechanisms by Which Benralizumab Suppresses IgE Expression in Human B Cells in Humanized Mice. Allergy 78, no. 12 (2023): 3271–3273.
    pubmed: 37814937
  37. Contoli M, Santus P, Menzella F. Effects of Anti‐IL5 Biological Treatments on Blood IgE Levels in Severe Asthmatic Patients: A Real‐Life Multicentre Study (BIONIGE). Clinical and Translational Allergy 12, no. 4 (2022): e12143.
    pmc: PMC8988861pubmed: 35423001
  38. Hitoshi Y, Yamaguchi N, Mita S. Distribution of IL‐5 Receptor‐Positive B Cells. Expression of IL‐5 Receptor on Ly‐1(CD5)+ B Cells. Journal of Immunology 144, no. 11 (1990): 4218–4225.
    pubmed: 1692859
  39. Hitoshi Y, Sonoda E, Kikuchi Y, Yonehara S, Nakauchi H, Takatsu K. IL‐5 Receptor Positive B Cells, but Not Eosinophils, Are Functionally and Numerically Influenced in Mice Carrying the X‐Linked Immune Defect. International Immunology 5, no. 9 (1993): 1183–1190.
    pubmed: 8241057
  40. Kolbeck R, Kozhich A, Koike M. MEDI‐563, a Humanized Anti‐IL‐5 Receptor Alpha mAb With Enhanced Antibody‐Dependent Cell‐Mediated Cytotoxicity Function. Journal of Allergy and Clinical Immunology 125, no. 6 (2010): 1344–1353.e2.
    pubmed: 20513525
  41. Takatsu K. Interleukin‐5 and IL‐5 Receptor in Health and Diseases. Proceedings of the Japan Academy. Series B, Physical and Biological Sciences 87, no. 8 (2011): 463–485.
    pmc: PMC3313690pubmed: 21986312
  42. Gorski SA, Lawrence MG, Hinkelman A. Expression of IL‐5 Receptor Alpha by Murine and Human Lung Neutrophils. PLoS One 14, no. 8 (2019): e0221113.
    pmc: PMC6695150pubmed: 31415658
  43. Dahl C, Hoffmann HJ, Saito H, Schiotz PO. Human Mast Cells Express Receptors for IL‐3, IL‐5 and GM‐CSF; a Partial Map of Receptors on Human Mast Cells Cultured In Vitro. Allergy 59, no. 10 (2004): 1087–1096.
    pubmed: 15355468
  44. Wilson TM, Maric I, Shukla J. IL‐5 Receptor Alpha Levels in Patients With Marked Eosinophilia or Mastocytosis. Journal of Allergy and Clinical Immunology 128, no. 5 (2011): 1086–1092.e1–3.
    pmc: PMC3205313pubmed: 21762978
  45. Steven Eck MC, Sinibaldi D, White W. Benralizumab Effect on Blood Basophil Counts in Adults With Uncontrolled Asthma. European Respiratory Journal 44 (2014): P297.
  46. Lommatzsch M, Marchewski H, Schwefel G, Stoll P, Virchow JC, Bratke K. Benralizumab Strongly Reduces Blood Basophils in Severe Eosinophilic Asthma. Clinical and Experimental Allergy 50, no. 11 (2020): 1267–1269.
    pubmed: 32762056
  47. Jebbawi F, Chemnitzer A, Dietrich M. Cytokines and Chemokines Skin Gene Expression in Correlation With Immune Cells in Blood and Severity in Equine Insect Bite Hypersensitivity. Frontiers in Immunology 15 (2024): 1414891.
    pmc: PMC11284025pubmed: 39076967
  48. Raza F, Babasyan S, Larson EM, Freer HS, Schnabel CL, Wagner B. Peripheral Blood Basophils Are the Main Source for Early Interleukin‐4 Secretion Upon In Vitro Stimulation With Culicoides Allergen in Allergic Horses. PLoS One 16, no. 5 (2021): e0252243.
    pmc: PMC8153460pubmed: 34038479
  49. Guo L, Hu‐Li J, Paul WE. Probabilistic Regulation of IL‐4 Production in Th2 Cells: Accessibility at the Il4 Locus. Immunity 20, no. 2 (2004): 193–203.
    pubmed: 14975241
  50. Zhu J. T Helper 2 (Th2) Cell Differentiation, Type 2 Innate Lymphoid Cell (ILC2) Development and Regulation of Interleukin‐4 (IL‐4) and IL‐13 Production. Cytokine 75, no. 1 (2015): 14–24.
    pmc: PMC4532589pubmed: 26044597
  51. Akbari O, Stock P, Meyer E. Essential Role of NKT Cells Producing IL‐4 and IL‐13 in the Development of Allergen‐Induced Airway Hyperreactivity. Nature Medicine 9, no. 5 (2003): 582–588.
    pubmed: 12669034
  52. Yoshimoto T. The Hunt for the Source of Primary Interleukin‐4: How we Discovered That Natural Killer T Cells and Basophils Determine T Helper Type 2 Cell Differentiation In Vivo. Frontiers in Immunology 9 (2018): 716.
    pmc: PMC5924770pubmed: 29740428
  53. Noval Rivas M, Burton OT, Oettgen HC, Chatila T. IL‐4 Production by Group 2 Innate Lymphoid Cells Promotes Food Allergy by Blocking Regulatory T‐Cell Function. Journal of Allergy and Clinical Immunology 138, no. 3 (2016): 801–811.e9.
    pmc: PMC5014699pubmed: 27177780
  54. Pelly VS, Kannan Y, Coomes SM. IL‐4‐Producing ILC2s Are Required for the Differentiation of T(H)2 Cells Following Heligmosomoides Polygyrus Infection. Mucosal Immunology 9, no. 6 (2016): 1407–1417.
    pmc: PMC5257265pubmed: 26883724
  55. McLeod JJ, Baker B, Ryan JJ. Mast Cell Production and Response to IL‐4 and IL‐13. Cytokine 75, no. 1 (2015): 57–61.
    pmc: PMC4532630pubmed: 26088754
  56. Weiss DL, Brown MA. Regulation of IL‐4 Production in Mast Cells: A Paradigm for Cell‐Type‐Specific Gene Expression. Immunological Reviews 179 (2001): 35–47.
    pubmed: 11292025
  57. Bjerke T, Gaustadnes M, Nielsen S. Human Blood Eosinophils Produce and Secrete Interleukin 4. Respiratory Medicine 90, no. 5 (1996): 271–277.
    pubmed: 9499811
  58. Goh YP, Henderson NC, Heredia JE. Eosinophils Secrete IL‐4 to Facilitate Liver Regeneration. Proceedings of the National Academy of Sciences of the United States of America 110, no. 24 (2013): 9914–9919.
    pmc: PMC3683773pubmed: 23716700
  59. Guth C, Schumacher PP, Vijayakumar A. Eosinophils Are an Endogenous Source of Interleukin‐4 During Filarial Infections and Contribute to the Development of an Optimal T Helper 2 Response. Journal of Innate Immunity 16, no. 1 (2024): 159–172.
    pmc: PMC10932553pubmed: 38354709
  60. Kasaian MT, Clay MJ, Happ MP, Garman RD, Hirani S, Luqman M. IL‐4 Production by Allergen‐Stimulated Primary Cultures: Identification of Basophils as the Major IL‐4‐Producing Cell Type. International Immunology 8, no. 8 (1996): 1287–1297.
    pubmed: 8918698
  61. Min B, Prout M, Hu‐Li J. Basophils Produce IL‐4 and Accumulate in Tissues After Infection With a Th2‐Inducing Parasite. Journal of Experimental Medicine 200, no. 4 (2004): 507–517.
    pmc: PMC2211939pubmed: 15314076
  62. van Panhuys N, Prout M, Forbes E, Min B, Paul WE, Le Gros G. Basophils Are the Major Producers of IL‐4 During Primary Helminth Infection. Journal of Immunology 186, no. 5 (2011): 2719–2728.
    pmc: PMC3488853pubmed: 21270410
  63. Nagata K, Hirai H, Tanaka K. CRTH2, an Orphan Receptor of T‐Helper‐2‐Cells, Is Expressed on Basophils and Eosinophils and Responds to Mast Cell‐Derived Factor(s). FEBS Letters 459, no. 2 (1999): 195–199.
    pubmed: 10518017
  64. Sullivan BM, Liang HE, Bando JK. Genetic Analysis of Basophil Function In Vivo. Nature Immunology 12, no. 6 (2011): 527–535.
    pmc: PMC3271435pubmed: 21552267
  65. Eckl‐Dorna J, Ellinger A, Blatt K. Basophils Are Not the Key Antigen‐Presenting Cells in Allergic Patients. Allergy 67, no. 5 (2012): 601–608.
    pmc: PMC4601523pubmed: 22335568
  66. Kitzmuller C, Nagl B, Deifl S. Human Blood Basophils Do Not Act as Antigen‐Presenting Cells for the Major Birch Pollen Allergen Bet v 1. Allergy 67, no. 5 (2012): 593–600.
    pubmed: 22188598
  67. Sokol C L, Chu N Q, Yu S, Nish S A, Laufer T M, Medzhitov R. Basophils Function as Antigen‐Presenting Cells for an Allergen‐Induced T Helper Type 2 Response. Nature Immunology 10, no. 7 (2009): 713–720.
    pmc: PMC3252751pubmed: 19465907
  68. Wagner B, Stokol T, Ainsworth D M. Induction of Interleukin‐4 Production in Neonatal IgE+ Cells After Crosslinking of Maternal IgE. Developmental and Comparative Immunology 34, no. 4 (2010): 436–444.
    pubmed: 19995577
  69. Del Prete G, Maggi E, Parronchi P. IL‐4 Is an Essential Factor for the IgE Synthesis Induced In Vitro by Human T Cell Clones and Their Supernatants. Journal of Immunology 140, no. 12 (1988): 4193–4198.
    pubmed: 2967330
  70. Pene J, Rousset F, Briere F. IgE Production by Normal Human Lymphocytes Is Induced by Interleukin 4 and Suppressed by Interferons Gamma and Alpha and Prostaglandin E2. Proceedings of the National Academy of Sciences of the United States of America 85, no. 18 (1988): 6880–6884.
    pmc: PMC282082pubmed: 2970644
  71. Pene J, Rousset F, Briere F. IgE Production by Normal Human B Cells Induced by Alloreactive T Cell Clones Is Mediated by IL‐4 and Suppressed by IFN‐Gamma. Journal of Immunology 141, no. 4 (1988): 1218–1224.
    pubmed: 3135324
  72. Sarfati M, Delespesse G. Possible Role of Human Lymphocyte Receptor for IgE (CD23) or Its Soluble Fragments in the In Vitro Synthesis of Human IgE. Journal of Immunology 141, no. 7 (1988): 2195–2199.
    pubmed: 2971721
  73. Vercelli D, Jabara H H, Arai K, Geha R S. Induction of Human IgE Synthesis Requires Interleukin 4 and T/B Cell Interactions Involving the T Cell Receptor/CD3 Complex and MHC Class II Antigens. Journal of Experimental Medicine 169, no. 4 (1989): 1295–1307.
    pmc: PMC2189234pubmed: 2522501
  74. Lebman D A, Coffman R L. Interleukin 4 Causes Isotype Switching to IgE in T Cell‐Stimulated Clonal B Cell Cultures. Journal of Experimental Medicine 168, no. 3 (1988): 853–862.
    pmc: PMC2189023pubmed: 3049907
  75. Strom L, Laurencikiene J, Miskiniene A, Severinson E. Characterization of CD40‐Dependent Immunoglobulin Class Switching. Scandinavian Journal of Immunology 49, no. 5 (1999): 523–532.
    pubmed: 10320646
  76. Mandler R, Chu C C, Paul W E, Max E E, Snapper C M. Interleukin 5 Induces S Mu‐S Gamma 1 DNA Rearrangement in B Cells Activated With Dextran‐Anti‐IgD Antibodies and Interleukin 4: A Three Component Model for Ig Class Switching. Journal of Experimental Medicine 178, no. 5 (1993): 1577–1586.
    pmc: PMC2191240pubmed: 8228808
  77. Mizoguchi C, Uehara S, Akira S, Takatsu K. IL‐5 Induces IgG1 Isotype Switch Recombination in Mouse CD38‐Activated sIgD‐Positive B Lymphocytes. Journal of Immunology 162, no. 5 (1999): 2812–2819.
    pubmed: 10072528
  78. Coffman R L, Lebman D A, Rothman P. Mechanism and Regulation of Immunoglobulin Isotype Switching. Advances in Immunology 54 (1993): 229–270.
    pubmed: 8379463
  79. Stavnezer J. Antibody Class Switching. Advances in Immunology 61 (1996): 79–146.
    pubmed: 8834495
  80. Kracker S, Radbruch A. Immunoglobulin Class Switching: In Vitro Induction and Analysis. Methods in Molecular Biology 271 (2004): 149–159.
    pubmed: 15146119
  81. Snapper C M, Rosas F R, Zelazowski P. B Cells Lacking RelB Are Defective in Proliferative Responses, but Undergo Normal B Cell Maturation to Ig Secretion and Ig Class Switching. Journal of Experimental Medicine 184, no. 4 (1996): 1537–1541.
    pmc: PMC2192806pubmed: 8879226
  82. Jabara H, Laouini D, Tsitsikov E. The Binding Site for TRAF2 and TRAF3 but Not for TRAF6 Is Essential for CD40‐Mediated Immunoglobulin Class Switching. Immunity 17, no. 3 (2002): 265–276.
    pubmed: 12354380
  83. Purkerson J M, Isakson P C. Interleukin 5 (IL‐5) Provides a Signal That Is Required in Addition to IL‐4 for Isotype Switching to Immunoglobulin (Ig) G1 and IgE. Journal of Experimental Medicine 175, no. 4 (1992): 973–982.
    pmc: PMC2119169pubmed: 1552290
  84. Kung T T, Stelts D M, Zurcher J A. Involvement of IL‐5 in a Murine Model of Allergic Pulmonary Inflammation: Prophylactic and Therapeutic Effect of an Anti‐IL‐5 Antibody. American Journal of Respiratory Cell and Molecular Biology 13, no. 3 (1995): 360–365.
    pubmed: 7654390
  85. Brostrom H, Larsson A, Troedsson M. Allergic Dermatitis (Sweet Itch) of Icelandic Horses in Sweden: An Epidemiological Study. Equine Veterinary Journal 19, no. 3 (1987): 229–236.
    pubmed: 3608962
  86. Halldorsdottir S, Lazary S, Gunnarsson E, Larsen H J. Distribution of Leucocyte Antigens in Icelandic Horses Affected With Summer Eczema Compared to Non‐Affected Horses. Equine Veterinary Journal 23, no. 4 (1991): 300–302.
    pubmed: 1915232
  87. Lange S, Hamann H, Deegen E, Ohnesorge B, Distl O. Investigation of the Prevalence of Summer Eczema in Icelandic Horses in Northern Germany. Berliner und Münchener Tierärztliche Wochenschrift 118, no. 11–12 (2005): 481–489.
    pubmed: 16318272
  88. Bjornsdottir S, Sigvaldadottir J, Brostrom H, Langvad B, Sigurdsson A. Summer Eczema in Exported Icelandic Horses: Influence of Environmental and Genetic Factors. Acta Veterinaria Scandinavica 48, no. 1 (2006): 3.
    pmc: PMC1513129pubmed: 16987399
  89. Torsteinsdottir S, Scheidegger S, Baselgia S. A Prospective Study on Insect Bite Hypersensitivity in Horses Exported From Iceland Into Switzerland. Acta Veterinaria Scandinavica 60, no. 1 (2018): 69.
    pmc: PMC6215642pubmed: 30390694

Citations

This article has been cited 1 times.
  1. Wichtowska A, Olejnik M. Anti-Cytokine Drugs in the Treatment of Canine Atopic Dermatitis. Int J Mol Sci 2025 Nov 13;26(22).
    doi: 10.3390/ijms262210990pubmed: 41303472google scholar: lookup
Subscribe to our newsletter
Join 99,928 horse owners like you who receive our email updates on horse health and nutrition.