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Home / Equine Research Bank / BMC Vet Res / Modulatory role of regulatory T cells in a murine model of s...
BMC veterinary research2017; 13(1); 117; doi: 10.1186/s12917-017-1037-0

Modulatory role of regulatory T cells in a murine model of severe equine asthma.

Abstract: It is accepted that T regulatory cells (Treg) control different types of immune responses. In connection with this role, we have recently described an important increase in CD4+, CD25, Foxp3+ lymphocytes in the airway system of horses coursing with an exacerbation of severe equine asthma (EA). To explore the potential role of this population in the resolution of EA inflammation, we used a murine experimental model in which airway neutrophilic inflammation, which is similar to that observed in EA, is induced in mice by continual exposure to Aspergillus fumigatus contaminated hay. This model has the advantage that in mice we may induce a reduction of the Treg population using low doses of cyclophosphamide (Cy). Results: The results indicated that the percentage of Treg cells increased with allergen exposure, as in horses; and animals partially depleted of Treg cells by treatment with Cy showed increased airway inflammation, demonstrated by an increased percentage of neutrophils and specific immunoglobulins in bronchoalveolar lavage fluid (BALF). Furthermore, a histopathologic study of animals that were pretreated with Cy before antigenic challenge showed higher cellular infiltration in the lung and deeper remodeling changes in the bronchi, including epithelial and goblet cell hyperplasia as well as airway smooth muscle hypertrophy. Conclusions: In this murine model of EA, the reduced number and function of Treg induced by low doses of Cy, which directly correlates with increased airway inflammation and lung infiltration, indicates that Treg may play a major role in the regulation and resolution of EA.
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Publication Date: 2017-04-28 PubMed ID: 28454585PubMed Central: PMC5410054DOI: 10.1186/s12917-017-1037-0Google Scholar: Lookup
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Summary

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This research article investigates the role of T regulatory cells (Treg) in controlling inflammation in severe equine asthma (EA), using a mouse model exposed to allergens. The study finds that reducing the Treg population results in increased airway inflammation and lung infiltration, suggesting that Treg plays a significant role in managing and resolving EA.

Objective of the Study

  • The goal of this study was to understand the role of T regulatory cells (Treg) in the resolution of severe equine asthma (EA). The researchers hypothesized that Treg cells play a crucial role in moderating immune responses, including the inflammation present in EA.

Study Design

  • The researchers used a murine (mouse) model for their experiment, where the mice were continually exposed to Aspergillus fumigatus, an allergen present in hay. This allergen induces an inhalation threat similar to EA in horses.
  • The model was designed to mimic the effects of EA, allowing researchers to manipulate the Treg population through the administration of low doses of cyclophosphamide (Cy), a drug known to decrease Treg cells.

Results of the Study

  • The study results indicated that continuous allergen exposure increased the percentage of Treg cells, mirroring the effects seen in horses suffering from EA.
  • Mice that received treatment with Cy, resulting in a partial depletion of Treg cells, displayed increased airway inflammation. This inflammation was evidenced by a higher percentage of neutrophils and specific immunoglobulins in bronchoalveolar lavage fluid (BALF), which is a fluid derived from the lungs.
  • A histopathological examination of mice pretreated with Cy before allergen exposure showed increased cellular infiltration in the lungs and more extensive changes in the bronchi, including epithelial and goblet cell hyperplasia and airway smooth muscle hypertrophy.

Conclusion of the Study

  • The study concluded that Treg cells play a major role in regulating and resolving the inflammation associated with EA. The reduction of Treg cells, facilitated by low doses of Cy, correlated with increased airway inflammation and lung infiltration.
  • This research suggests potential future treatment approaches for EA could involve therapeutic methods to increase the population of Treg cells or enhance their function.

Cite This Article

APA
Henríquez C, Morán G, Carrasco C, Sarmiento J, Barría M, Folch H, Uberti B. (2017). Modulatory role of regulatory T cells in a murine model of severe equine asthma. BMC Vet Res, 13(1), 117. https://doi.org/10.1186/s12917-017-1037-0

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 13
Issue: 1
Pages: 117
PII: 117

Researcher Affiliations

Henríquez, Claudio
  • Pharmacology and Morphophysiology Department, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile.
Morán, Gabriel
  • Pharmacology and Morphophysiology Department, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile. gmoran@uach.cl.
Carrasco, Cristian
  • Pathology Department, Regional Hospital of Valdivia, Valdivia, Chile.
Sarmiento, José
  • Physiology Department, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile.
Barría, Miguel
  • Immunology Department, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile.
Folch, Hugo
  • Immunology Department, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile.
Uberti, Benjamin
  • Veterinary Clinical Sciences Department, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile.

MeSH Terms

  • Acute Disease
  • Allergens / immunology
  • Animal Feed / microbiology
  • Animals
  • Aspergillus fumigatus / immunology
  • Asthma / immunology
  • Asthma / veterinary
  • Bronchoalveolar Lavage Fluid / cytology
  • Disease Models, Animal
  • Female
  • Horse Diseases / immunology
  • Horses
  • Mice
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / physiology

References

This article includes 33 references
  1. Bullone M, Lavoie JP. Asthma "of horses and men"--how can equine heaves help us better understand human asthma immunopathology and its functional consequences?. Mol Immunol 2015 Jul;66(1):97-105.
    doi: 10.1016/j.molimm.2014.12.005pubmed: 25547716google scholar: lookup
  2. Couëtil LL, Cardwell JM, Gerber V, Lavoie JP, Léguillette R, Richard EA. Inflammatory Airway Disease of Horses--Revised Consensus Statement.. J Vet Intern Med 2016 Mar-Apr;30(2):503-15.
    doi: 10.1111/jvim.13824pmc: PMC4913592pubmed: 26806374google scholar: lookup
  3. Pirie RS, Couëtil LL, Robinson NE, Lavoie JP. Equine asthma: An appropriate, translational and comprehendible terminology?. Equine Vet J 2016 Jul;48(4):403-5.
    doi: 10.1111/evj.12586pubmed: 27292020google scholar: lookup
  4. Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an asthma-like disease of horses.. Respirology 2011 Oct;16(7):1027-46.
    doi: 10.1111/j.1440-1843.2011.02033.xpubmed: 21824219google scholar: lookup
  5. Léguillette R. Recurrent airway obstruction--heaves.. Vet Clin North Am Equine Pract 2003 Apr;19(1):63-86, vi.
    doi: 10.1016/S0749-0739(02)00067-6pubmed: 12747662google scholar: lookup
  6. Ha TY. The role of regulatory T cells in cancer.. Immune Netw 2009 Dec;9(6):209-35.
    doi: 10.4110/in.2009.9.6.209pmc: PMC2816955pubmed: 20157609google scholar: lookup
  7. Shevach EM. Regulatory T cells in autoimmmunity*.. Annu Rev Immunol 2000;18:423-49.
    doi: 10.1146/annurev.immunol.18.1.423pubmed: 10837065google scholar: lookup
  8. Akdis M, Blaser K, Akdis CA. T regulatory cells in allergy: novel concepts in the pathogenesis, prevention, and treatment of allergic diseases.. J Allergy Clin Immunol 2005 Nov;116(5):961-8; quiz 969.
    doi: 10.1016/j.jaci.2005.09.004pubmed: 16275361google scholar: lookup
  9. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.. J Immunol 1995 Aug 1;155(3):1151-64.
    pubmed: 7636184
  10. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.. Nat Immunol 2003 Apr;4(4):330-6.
    doi: 10.1038/ni904pubmed: 12612578google scholar: lookup
  11. Bacchetta R, Gambineri E, Roncarolo MG. Role of regulatory T cells and FOXP3 in human diseases.. J Allergy Clin Immunol 2007 Aug;120(2):227-35; quiz 236-7.
    doi: 10.1016/j.jaci.2007.06.023pubmed: 17666212google scholar: lookup
  12. Banerjee A, Vasanthakumar A, Grigoriadis G. Modulating T regulatory cells in cancer: how close are we?. Immunol Cell Biol 2013 May;91(5):340-9.
    doi: 10.1038/icb.2013.12pubmed: 23567897google scholar: lookup
  13. Beres AJ, Drobyski WR. The role of regulatory T cells in the biology of graft versus host disease.. Front Immunol 2013;4:163.
    doi: 10.3389/fimmu.2013.00163pmc: PMC3690651pubmed: 23805140google scholar: lookup
  14. Cao T, Wenzel SE, Faubion WA, Harriman G, Li L. Enhanced suppressive function of regulatory T cells from patients with immune-mediated diseases following successful ex vivo expansion.. Clin Immunol 2010 Sep;136(3):329-37.
    doi: 10.1016/j.clim.2010.04.014pmc: PMC3891466pubmed: 20472506google scholar: lookup
  15. Nishimoto T, Kuwana M. CD4+CD25+Foxp3+ regulatory T cells in the pathophysiology of immune thrombocytopenia.. Semin Hematol 2013 Jan;50 Suppl 1:S43-9.
    doi: 10.1053/j.seminhematol.2013.03.018pubmed: 23664516google scholar: lookup
  16. Palomares O, Yaman G, Azkur AK, Akkoc T, Akdis M, Akdis CA. Role of Treg in immune regulation of allergic diseases.. Eur J Immunol 2010 May;40(5):1232-40.
    doi: 10.1002/eji.200940045pubmed: 20148422google scholar: lookup
  17. Wainwright DA, Dey M, Chang A, Lesniak MS. Targeting Tregs in Malignant Brain Cancer: Overcoming IDO.. Front Immunol 2013;4:116.
    doi: 10.3389/fimmu.2013.00116pmc: PMC3654236pubmed: 23720663google scholar: lookup
  18. Wing K, Sakaguchi S. Regulatory T cells exert checks and balances on self tolerance and autoimmunity.. Nat Immunol 2010 Jan;11(1):7-13.
    doi: 10.1038/ni.1818pubmed: 20016504google scholar: lookup
  19. Henríquez C, Perez B, Morales N, Sarmiento J, Carrasco C, Morán G, Folch H. Participation of T regulatory cells in equine recurrent airway obstruction.. Vet Immunol Immunopathol 2014 Apr 15;158(3-4):128-34.
    doi: 10.1016/j.vetimm.2013.12.005pubmed: 24503328google scholar: lookup
  20. Moran G, Ojeda G, Diedrichs K, Ortloff A, Barria M, Folch H. Inhalation of Aspergillus fumigatus spores induces airway inflammation in mice in a similar manner as observed in recurrent airway obstruction in horses.. Arch Med Vet 2011;43:163–171.
    doi: 10.4067/S0301-732X2011000200009google scholar: lookup
  21. Gerber V, Tessier C, Marti E. Genetics of upper and lower airway diseases in the horse.. Equine Vet J 2015 Jul;47(4):390-7.
    doi: 10.1111/evj.12289pubmed: 24773614google scholar: lookup
  22. Barbon CM, Yang M, Wands GD, Ramesh R, Slusher BS, Hedley ML, Luby TM. Consecutive low doses of cyclophosphamide preferentially target Tregs and potentiate T cell responses induced by DNA PLG microparticle immunization.. Cell Immunol 2010;262(2):150-61.
    doi: 10.1016/j.cellimm.2010.02.007pubmed: 20206921google scholar: lookup
  23. Askenase PW, Hayden BJ, Gershon RK. Augmentation of delayed-type hypersensitivity by doses of cyclophosphamide which do not affect antibody responses.. J Exp Med 1975 Mar 1;141(3):697-702.
    doi: 10.1084/jem.141.3.697pmc: PMC2189708pubmed: 1117258google scholar: lookup
  24. Folch H, Lopetegui F, Stegmeier E. Abrogation of antigenic competition phenomenon by a low dose of cyclophosphamide.. Zentralbl Veterinarmed B 1980;27(2):139-43.
    doi: 10.1111/j.1439-0450.1980.tb01647.xpubmed: 6451120google scholar: lookup
  25. Audia S, Nicolas A, Cathelin D, Larmonier N, Ferrand C, Foucher P, Fanton A, Bergoin E, Maynadie M, Arnould L, Bateman A, Lorcerie B, Solary E, Chauffert B, Bonnotte B. Increase of CD4+ CD25+ regulatory T cells in the peripheral blood of patients with metastatic carcinoma: a Phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4+ CD25+ T lymphocytes.. Clin Exp Immunol 2007 Dec;150(3):523-30.
    doi: 10.1111/j.1365-2249.2007.03521.xpmc: PMC2219383pubmed: 17956583google scholar: lookup
  26. Rech AJ, Vonderheide RH. Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells.. Ann N Y Acad Sci 2009 Sep;1174:99-106.
    doi: 10.1111/j.1749-6632.2009.04939.xpubmed: 19769742google scholar: lookup
  27. Schabowsky RH, Madireddi S, Sharma R, Yolcu ES, Shirwan H. Targeting CD4+CD25+FoxP3+ regulatory T-cells for the augmentation of cancer immunotherapy.. Curr Opin Investig Drugs 2007 Dec;8(12):1002-8.
    pubmed: 18058571
  28. Zhao L, Sun L, Wang H, Ma H, Liu G, Zhao Y. Changes of CD4+CD25+Foxp3+ regulatory T cells in aged Balb/c mice.. J Leukoc Biol 2007 Jun;81(6):1386-94.
    doi: 10.1189/jlb.0506364pubmed: 17369496google scholar: lookup
  29. Schenk U, Frascoli M, Proietti M, Geffers R, Traggiai E, Buer J, Ricordi C, Westendorf AM, Grassi F. ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors.. Sci Signal 2011 Mar 1;4(162):ra12.
    doi: 10.1126/scisignal.2001270pubmed: 21364186google scholar: lookup
  30. Lutsiak ME, Semnani RT, De Pascalis R, Kashmiri SV, Schlom J, Sabzevari H. Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide.. Blood 2005 Apr 1;105(7):2862-8.
    doi: 10.1182/blood-2004-06-2410pubmed: 15591121google scholar: lookup
  31. Curotto de Lafaille MA, Lafaille JJ. CD4(+) regulatory T cells in autoimmunity and allergy.. Curr Opin Immunol 2002 Dec;14(6):771-8.
    doi: 10.1016/S0952-7915(02)00408-9pubmed: 12413528google scholar: lookup
  32. Cooper JA Jr, Merrill WW, Reynolds HY. Cyclophosphamide modulation of bronchoalveolar cellular populations and macrophage oxidative metabolism. Possible mechanisms of pulmonary pharmacotoxicity.. Am Rev Respir Dis 1986 Jul;134(1):108-14.
    pubmed: 3014931doi: 10.1164/arrd.1986.134.1.108google scholar: lookup
  33. Pirie RS. Recurrent airway obstruction: a review.. Equine Vet J 2014 May;46(3):276-88.
    doi: 10.1111/evj.12204pubmed: 24164473google scholar: lookup

Citations

This article has been cited 1 times.
  1. Marín-Prida J, Pavón-Fuentes N, Lagumersindez-Denis N, Camacho-Rodríguez H, García-Soca AM, Sarduy-Chávez RC, Vieira ÉLM, Carvalho-Tavares J, Falcón-Cama V, Fernández-Massó JR, Hernández-González I, Martínez-Donato G, Guillén-Nieto G, Pentón-Arias E, Teixeira MM, Pentón-Rol G. Anti-inflammatory mechanisms and pharmacological actions of phycocyanobilin in a mouse model of experimental autoimmune encephalomyelitis: A therapeutic promise for multiple sclerosis.. Front Immunol 2022;13:1036200.
    doi: 10.3389/fimmu.2022.1036200pubmed: 36405721google scholar: lookup
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