Peripheral blood basophils are the main source for early interleukin-4 secretion upon in vitro stimulation with Culicoides allergen in allergic horses.
Abstract: Interleukin-4 (IL-4) is a key cytokine secreted by type 2 T helper (Th2) cells that orchestrates immune responses during allergic reactions. Human and mouse studies additionally suggest that basophils have a unique role in the regulation of allergic diseases by providing initial IL-4 to drive T cell development towards the Th2 phenotype. Equine Culicoides hypersensitivity (CH) is a seasonal immunoglobulin E (IgE)-mediated allergic dermatitis in horses in response to salivary allergens from Culicoides (Cul) midges. Here, we analyzed IL-4 production in peripheral blood mononuclear cells (PBMC) of CH affected (n = 8) and healthy horses (n = 8) living together in an environment with natural Cul exposure. During Cul exposure when allergic horses had clinical allergy, IL-4 secretion from PBMC after stimulation with Cul extract was similar between healthy and CH affected horses. In contrast, allergic horses had higher IL-4 secretion from PBMC than healthy horses during months without allergen exposure. In addition, allergic horses had increased percentages of IL-4+ cells after Cul stimulation compared to healthy horses, while both groups had similar percentages of IL-4+ cells following IgE crosslinking. The IL-4+ cells were subsequently characterized using different cell surface markers as basophils, while very few allergen-specific CD4+ cells were detected in PBMC after Cul extract stimulation. Similarly, IgE crosslinking by anti-IgE triggered basophils to produce IL-4 in all horses. PMA/ionomycin consistently induced high percentages of IL-4+ Th2 cells in both groups confirming that T cells of all horses studied were capable of IL-4 production. In conclusion, peripheral blood basophils produced high amounts of IL-4 in allergic horses after stimulation with Cul allergens, and allergic horses also maintained higher basophil percentages throughout the year than healthy horses. These new findings suggest that peripheral blood basophils may play a yet underestimated role in innate IL-4 production upon allergen activation in horses with CH. Basophil-derived IL-4 might be a crucial early signal for immune induction, modulating of immune responses towards Th2 immunity and IgE production.
Publication Date: 2021-05-26 PubMed ID: 34038479PubMed Central: PMC8153460DOI: 10.1371/journal.pone.0252243Google Scholar: Lookup
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Summary
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The research article discusses how basophils (a type of white blood cell) in horses are a main source of an immune system protein (interleukin-4 or IL-4) upon exposure to allergens from Culicoides midges. This finding could potentially provide a new understanding of the role these cells play in immune system reactions towards allergens.
Study Overview
- The study focuses on equine Culicoides hypersensitivity (CH), a seasonal allergic dermatitis in horses caused by salivary allergens from Culicoides midges. The allergic reaction is mediated by immunoglobulin E (IgE), an antibody produced by the immune system.
- The researchers examined the production of a specific cytokine, interleukin-4 (IL-4) — an important respondent in allergic reactions — in the peripheral blood mononuclear cells (PBMC) of horses affected by CH compared to healthy horses.
Main Findings
- The research found that, when exposed to Culicoides allergens, the level of IL-4 produced by PBMC in allergic horses was similar to the amount produced by healthy horses.
- However, during the months when allergens were not present, allergic horses secreted more IL-4 compared to healthy horses. This elevated production was maintained throughout the year in allergic horses.
- The research also determined that allergic horses had an increased percentage of cells producing IL-4 after being stimulated by Culicoides allergens.
- The cells secreting IL-4 were identified as basophils — a type of white blood cell — while very few allergen-specific CD4+ cells were detected.
- The increased production of IL-4 in allergic horses was present in all basophils, regardless if they were triggered by allergen-related IgE or by synthetic agents PMA/Ionomycin.
Conclusions
- The research concludes that blood basophils in horses produced large amounts of IL-4 after exposure to Culicoides allergens.
- This conclusion suggests that these basophils might play a more significant role in the early immune response to allergens in horses with CH than initially estimated.
- Specifically, the production of basophil-derived IL-4 could be a crucial early signal for immune system activation, leading to a shift towards type 2 T helper (Th2) immunity and IgE production when encountering allergens.
Cite This Article
APA
Raza F, Babasyan S, Larson EM, Freer HS, Schnabel CL, Wagner B.
(2021).
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(5), e0252243.
https://doi.org/10.1371/journal.pone.0252243 Publication
Researcher Affiliations
- Departments of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
- Departments of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
- Departments of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
- Departments of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
- Departments of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
- Departments of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
MeSH Terms
- Allergens / pharmacology
- Animals
- Basophils / drug effects
- Basophils / metabolism
- Cells, Cultured
- Ceratopogonidae / immunology
- Horses
- Interleukin-4 / metabolism
- Phenotype
Conflict of Interest Statement
The authors have declared that no competing interests exist.
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Citations
This article has been cited 4 times.- Simonin EM, Wagner B. IgE-binding monocytes upregulate the coagulation cascade in allergic horses. Genes Immun 2023 Jun;24(3):130-138.
- Gressler AE, Lübke S, Wagner B, Arnold C, Lohmann KL, Schnabel CL. Comprehensive Flow Cytometric Characterization of Bronchoalveolar Lavage Cells Indicates Comparable Phenotypes Between Asthmatic and Healthy Horses But Functional Lymphocyte Differences. Front Immunol 2022;13:896255.
- Schnabel CL, Fletemeyer B, Lübke S, Marti E, Wagner B, Alber G. CD154 Expression Indicates T Cell Activation Following Tetanus Toxoid Vaccination of Horses. Front Immunol 2022;13:805026.
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