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International archives of allergy and immunology2007; 144(4); 325-337; doi: 10.1159/000106459

Modulation of allergy incidence in icelandic horses is associated with a change in IL-4-producing T cells.

Abstract: Equine insect bite hypersensitivity (IBH) is an immediate-type hypersensitivity reaction provoked by insect-derived allergens. Icelandic horses living in Iceland do not have IBH due to absence of relevant insects, but acquire it at high frequency after being imported to mainland Europe. In contrast, their offspring born in mainland Europe has reduced IBH incidence. T helper 1 (Th1) and Th2 cells and cytokines were determined in Icelandic horses born in Iceland and on the continent and which either have IBH or are healthy. Methods: Peripheral blood mononuclear cells (PBMC) from these horses were stimulated for 18 h during summer and winter with polyclonal T cell stimuli, IBH allergen(s) or irrelevant allergen(s). Cells were analysed by flow cytometry for interferon-gamma (IFN-gamma) and interleukin-4 (IL-4); RNA was analysed for IFN-gamma, IL-4, IL-5 and IL-13 mRNA. Results: During summer, but not during winter, IBH PBMC stimulated polyclonally showed reduced IFN-gamma mRNA and IFN-gamma-producing cells when compared with those of healthy horses, regardless of origin. PBMC stimulated polyclonally or with IBH allergen showed increased IL-4 mRNA levels and higher numbers of IL-4-producing cells when born in Iceland or showing IBH symptoms. IL-5 and IL-13 mRNA were modulated neither by disease nor by origin. Abrogation of IL-4 production in healthy horses born in mainland Europe may be due, at least in part, to IL-10. There was an increased level of IL-10 in supernatants from PBMC of healthy horses born in mainland Europe and stimulated polyclonally or with IBH allergen. Conclusions: Modulation of IBH incidence is governed by altered Th1/Th2 ratio, which might be influenced by IL-10.
Publication Date: 2007-07-02 PubMed ID: 17671392DOI: 10.1159/000106459Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research studied a type of allergic reaction in horses known as Equine Insect Bite Hypersensitivity (IBH), which was found to be influenced by T cell changes, particularly in relation to a cytokine known as IL-4.

Study Background

  • The study was triggered by the observation that Icelandic horses born and raised in Iceland did not exhibit IBH, an allergic reaction caused by reactions to insect bites.
  • However, upon migrating to mainland Europe, a high percentage of the horses developed the condition.
  • Interestingly, the offspring of these transplanted Icelandic horses that are born in mainland Europe have a lower likelihood of contracting IBH.

Methodology

  • The scientists examined the T helper cells (Th1 and Th2) and their related cytokines within these horses, both those originating from Iceland and those born in mainland Europe.
  • Cytokines are proteins that play key roles in regulating immune responses.
  • The study focused particularly on four cytokines – IFN-gamma, IL-4, IL-5 and IL-13 – and their mRNA counterparts.
  • The horses’ Peripheral blood mononuclear cells (PBMC) were isolated and subjected to different stimulations involving T cell stimuli, IBH allergens, and unrelated allergens.
  • The reactions of these cells in summer and winter were analyzed via flow cytometry and mRNA analysis.

Results and Findings

  • The research found that horses presenting with IBH (regardless of their place of birth) showed a decrease in IFN-gamma mRNA and IFN-gamma-producing cells in the summer months.
  • This was not observed in the winter months, indicating a seasonal effect on the immune response.
  • Simultaneously, an increase in IL-4 mRNA levels and IL-4-producing cells were observed when horses were either born in Iceland or exhibiting IBH symptoms.
  • However, there were no noticeable changes in IL-5 and IL-13 mRNA irrespective of the disease status or origin of the horses.
  • The researchers also found that in healthy horses born in mainland Europe, IL-4 production was seemingly inhibited, possibly by the action of another cytokine known as IL-10.
  • High IL-10 levels were found in the blood cells of healthy horses born in mainland Europe, potential evidence of IL-10’s role in countering IBH.

Conclusion

  • The study concluded that the incidence of IBH in horses might be regulated by alterations in Th1/Th2 ratios, with the cytokine IL-10 possibly playing a major role.
  • This provides new insights into the pathogenesis of equine IBH and indicates potential directions for future research, such as studying the role of IL-10 in preventing allergic reactions.

Cite This Article

APA
Hamza E, Doherr MG, Bertoni G, Jungi TW, Marti E. (2007). Modulation of allergy incidence in icelandic horses is associated with a change in IL-4-producing T cells. Int Arch Allergy Immunol, 144(4), 325-337. https://doi.org/10.1159/000106459

Publication

ISSN: 1423-0097
NlmUniqueID: 9211652
Country: Switzerland
Language: English
Volume: 144
Issue: 4
Pages: 325-337

Researcher Affiliations

Hamza, E
  • Institute of Veterinary Virology, University of Bern, Bern, Switzerland.
Doherr, M G
    Bertoni, G
      Jungi, T W
        Marti, E

          MeSH Terms

          • Allergens / immunology
          • Animals
          • Cells, Cultured
          • Ceratopogonidae / immunology
          • Cytokines / genetics
          • Cytokines / immunology
          • Female
          • Horse Diseases / epidemiology
          • Horse Diseases / etiology
          • Horse Diseases / immunology
          • Horses
          • Hypersensitivity, Immediate / epidemiology
          • Hypersensitivity, Immediate / etiology
          • Hypersensitivity, Immediate / immunology
          • Hypersensitivity, Immediate / veterinary
          • Incidence
          • Insect Bites and Stings / immunology
          • Insect Bites and Stings / veterinary
          • Leukocytes, Mononuclear / immunology
          • Male
          • RNA, Messenger / metabolism
          • Seasons
          • T-Lymphocytes / immunology

          Citations

          This article has been cited 10 times.
          1. Bao S, Lu X, Xiang S, Hou X. Establishment of a mouse allergy model for Culicoides (Diptera: Ceratopogonidae). Vet Med Sci 2024 May;10(3):e1462.
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          2. Jonsdottir S, Fettelschoss V, Olomski F, Talker SC, Mirkovitch J, Rhiner T, Birkmann K, Thoms F, Wagner B, Bachmann MF, Kündig TM, Marti E, Fettelschoss-Gabriel A. Safety Profile of a Virus-Like Particle-Based Vaccine Targeting Self-Protein Interleukin-5 in Horses. Vaccines (Basel) 2020 May 9;8(2).
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          3. Cvitas I, Oberhänsli S, Leeb T, Dettwiler M, Müller E, Bruggman R, Marti EI. Investigating the epithelial barrier and immune signatures in the pathogenesis of equine insect bite hypersensitivity. PLoS One 2020;15(4):e0232189.
            doi: 10.1371/journal.pone.0232189pubmed: 32343720google scholar: lookup
          4. Mason VC, Schaefer RJ, McCue ME, Leeb T, Gerber V. eQTL discovery and their association with severe equine asthma in European Warmblood horses. BMC Genomics 2018 Aug 2;19(1):581.
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          5. Lehiy CJ, Reister-Hendricks LM, Ruder MG, McVey DS, Drolet BS. Physiological and immunological responses to Culicoides sonorensis blood-feeding: a murine model. Parasit Vectors 2018 Jun 20;11(1):358.
            doi: 10.1186/s13071-018-2935-0pubmed: 29925422google scholar: lookup
          6. Ziegler A, Everett H, Hamza E, Garbani M, Gerber V, Marti E, Steinbach F. Equine dendritic cells generated with horse serum have enhanced functionality in comparison to dendritic cells generated with fetal bovine serum. BMC Vet Res 2016 Nov 15;12(1):254.
            doi: 10.1186/s12917-016-0880-8pubmed: 27846835google scholar: lookup
          7. Hamza E, Mirkovitch J, Steinbach F, Marti E. Regulatory T cells in early life: comparative study of CD4+CD25high T cells from foals and adult horses. PLoS One 2015;10(3):e0120661.
            doi: 10.1371/journal.pone.0120661pubmed: 25790481google scholar: lookup
          8. Pacholewska A, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Gerber V, Leeb T, Jagannathan V. The transcriptome of equine peripheral blood mononuclear cells. PLoS One 2015;10(3):e0122011.
            doi: 10.1371/journal.pone.0122011pubmed: 25790166google scholar: lookup
          9. 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.
            doi: 10.1007/s11033-012-2408-zpubmed: 23275235google scholar: lookup
          10. 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.