Reduced incidence of insect-bite hypersensitivity in Icelandic horses is associated with a down-regulation of interleukin-4 by interleukin-10 and transforming growth factor-beta1.
Abstract: Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by IgE-mediated reactions to bites of insects of the genus Culicoides. IBH does not occur in Iceland due to the absence of Culicoides. However, Icelandic horses exported to mainland Europe as adults (1st generation) have a > or =50% incidence of developing IBH. In contrast, their progeny (2nd generation) has a <10% incidence of IBH. Here we show that peripheral blood mononuclear cells (PBMC) from Icelandic horses born in mainland Europe and belonging either to the IBH or healthy subgroup produce less interleukin (IL)-4 after polyclonal or allergen-specific stimulation when compared with counterparts from horses born in Iceland. We examined a role of IL-10 and transforming growth factor (TGF)-beta1 in down-regulation of IL-4 in healthy 2nd generation Icelandic horses. Supernatants of PBMC from 2nd generation healthy horses down-regulated the proportion of IL-4-producing cells and IL-4 production in stimulated cultures of PBMC from 1st generation IBH. This inhibition was mimicked by a combination of IL-10 and TGF-beta1 but not by the single cytokines. Cultures of stimulated PBMC of healthy 2nd generation horses produced a low level of IL-4, but IL-4 production was increased by anti-equine IL-10 and anti-human TGF-beta1. This shows for the first time that in horses, IL-10 and TGF-beta1 combined regulate IL-4 production in vitro. It is suggested that in this naturally occurring IgE-mediated allergy, IL-10 and TGF-beta1 have a role in the down-regulation of IL-4-induced allergen-specific Th2 cells, thereby reducing the incidence of IBH.
Publication Date: 2007-11-09 PubMed ID: 18082270DOI: 10.1016/j.vetimm.2007.10.018Google 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.
- Journal Article
- Research Support
- Non-U.S. Gov't
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.
The research investigates why Icelandic horses born and exported to Europe as adults are more likely to develop insect bite hypersensitivity (IBH), a form of allergic dermatitis caused by insect bites, than their locally born counterparts. Essentially, these exported horses trigger an interleukin-4 response to insect bites, causing an allergic reaction. However, their European-born progeny have a reduced incidence of IBH, which seems to be due to an interaction of interleukin-10 and transforming growth factor-beta1 down-regulating this reaction.
Understanding the Research
This study’s findings relate to the interplay between the immune response of horses to bites from insects of the genus Culicoides, specifically the production of interleukin-4 (IL-4), and how that may be regulated by both interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1).
- Insects from this genus are not present in Iceland, so Icelandic horses do not develop IBH naturally. However, when Icelandic horses are moved to mainland Europe as adults, they have a greater than or equal to 50% likelihood of developing IBH due to exposure to Culicoides insects.
- Interestingly, the progeny of these exported horses, born in Europe, have a less than 10% incidence of developing IBH. To study this, the researchers compared the immune response of both these groups to the insect allergen, focusing on the blood cells that mediate immune response (PBMCs).
- They found that PBMCs from both groups (IBH-affected and healthy) produced less IL-4, which is commonly associated with allergic response, when stimulated. However, PBMCs from the healthy European-born horses also exhibited down-regulation of IL-4 production, which is associated with a reduced incidence of IBH.
- Further investigation revealed that IL-10 and TGF-beta1, both involved in immune regulation, were crucial in this process. In combination, these two factors seemed to reduce the proportion of cells producing IL-4 and the production of IL-4 itself in stimulated PBMC cultures from the first-generation, IBH-affected horses.
- The study found this effect could not be replicated with either factor alone, suggesting that both IL-10 and TGF-beta1 are required for down-regulation. Conversely, the production of IL-4 was increased when IL-10 and TGF-beta1 were inhibited.
- This interplay between IL-10, TGF-beta1 and IL-4 is present in horses for the first time, suggesting a regulatory mechanism governing allergic reaction. The research suggests that in horses, IL-10 and TGF-beta1 play a role in the down-regulation of IL-4-induced, allergen-specific Th2 cells, leading to a reduction in IBH incidence.
Cite This Article
APA
Hamza E, Wagner B, Jungi TW, Mirkovitch J, Marti E.
(2007).
Reduced incidence of insect-bite hypersensitivity in Icelandic horses is associated with a down-regulation of interleukin-4 by interleukin-10 and transforming growth factor-beta1.
Vet Immunol Immunopathol, 122(1-2), 65-75.
https://doi.org/10.1016/j.vetimm.2007.10.018 Publication
Researcher Affiliations
- Institute of Veterinary Virology, Vetsuisse Faculty, University of Bern, Laenggassstrasse 122, CH-3001 Bern, Switzerland.
MeSH Terms
- Animals
- Down-Regulation
- Horses
- Hypersensitivity / prevention & control
- Insect Bites and Stings / immunology
- Interleukin-10 / physiology
- Interleukin-4 / antagonists & inhibitors
- Interleukin-4 / biosynthesis
- Transforming Growth Factor beta1 / physiology
Citations
This article has been cited 7 times.- Birras J, White SJ, Jonsdottir S, Novotny EN, Ziegler A, Wilson AD, Frey R, Torsteinsdottir S, Alcocer M, Marti E. First clinical expression of equine insect bite hypersensitivity is associated with co-sensitization to multiple Culicoides allergens. PLoS One 2021;16(11):e0257819.
- 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 2021;16(5):e0252243.
- Larson EM, Babasyan S, Wagner B. Phenotype and function of IgE-binding monocytes in equine Culicoides hypersensitivity. PLoS One 2020;15(5):e0233537.
- Verdon M, Lanz S, Rhyner C, Gerber V, Marti E. Allergen-specific immunoglobulin E in sera of horses affected with insect bite hypersensitivity, severe equine asthma or both conditions. J Vet Intern Med 2019 Jan;33(1):266-274.
- Pacholewska A, Jagannathan V, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Leeb T, Gerber V. Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma. PLoS One 2015;10(8):e0136103.
- Klumplerova M, Vychodilova L, Bobrova O, Cvanova M, Futas J, Janova E, Vyskocil M, Vrtkova I, Putnova L, Dusek L, Marti E, Horin P. Major histocompatibility complex and other allergy-related candidate genes associated with insect bite hypersensitivity in Icelandic horses. Mol Biol Rep 2013 Apr;40(4):3333-40.
- Hamza E, Gerber V, Steinbach F, Marti E. Equine CD4(+) CD25(high) T cells exhibit regulatory activity by close contact and cytokine-dependent mechanisms in vitro. Immunology 2011 Nov;134(3):292-304.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
