Quantitative analysis of CD4+CD25+FoxP3+ regulatory T-cells in canine atopic dermatitis in Korea

https://doi.org/10.17221/20/2019-VETMEDCitation:Lee D., Chung T., Park C. (2020): Quantitative analysis of CD4+CD25+FoxP3+ regulatory T-cells in canine atopic dermatitis in Korea. Veterinarni Medicina, 65: 250-257.
download PDF

Recently, it was suggested that CD4+CD25+FoxP3+ Tregs (Regulatory T-cells) exist in canine skin, although their numbers were not significantly different between healthy and atopic dogs. In this study, we investigated whether Treg frequencies correlate with the clinical features of canine atopic dermatitis (cAD). The goal of this study was to compare and analyse the numbers of the circulating Tregs in atopic and healthy dogs. In the peripheral blood mononuclear cells (PBMC) of healthy dogs, Tregs defined as CD4+CD25+FoxP3+ Tregs in the peripheral blood ranged from 0.3% to 1.5%. By contrast, in atopic dogs, the same population ranged from 0.7% to 8.8%. The percentage of CD4+CD25+FoxP3+ Tregs in gated CD4+ T-cells was significantly higher in the peripheral blood of dogs with atopic dermatitis (n = 9) than in the healthy controls (n = 8). The difference in the Treg levels (CD4+CD25+FoxP3+) (P = 0.012) between the atopic and the healthy groups was statistically significant. The circulating T-cells (phenotype CD4+CD25+FoxP3+ and CD4+FoxP3+) were increased significantly in the atopic dogs. The proportion of CD4+CD25+FoxP3+ Tregs of the atopic dogs decreased with advancing age. These findings suggest that changes in the Tregs may mediate the pathogenesis of CAD.

References:
Biller B, Elmslie R, Burnett R, Avery A, Dow S. Use of FoxP3 expression to identify regulatory T-cells in healthy dogs and dogs with cancer. Vet Immunol Immunopathol. 2007 Mar15;116(1-2):69-78. https://doi.org/10.1016/j.vetimm.2006.12.002
 
Favrot C, Steffan J, Seewald W, Picco F. A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis. Vet Dermatol. 2010 Feb;21(1):23-31. https://doi.org/10.1111/j.1365-3164.2009.00758.x
 
Gaspar K, Barath S, Nagy G, Mocsai G, Gyimesi E, Szodoray P, Irinyi B, Zeher M, Remenyik E, Szegedi A. Regulatory T-cell subsets with acquired functional impairment: important indicators of disease severity in atopic dermatitis. Acta Derm Venereol. 2015 Feb;95(2):151-5. https://doi.org/10.2340/00015555-1882
 
Hauck V, Hugli P, Meli ML, Rostaher A, Fischer N, Hofmann-Lehmann R, Favrot C. Increased numbers of FoxP3-expressing CD4+ CD25+ regulatory T-cells in peripheral blood from dogs with atopic dermatitis and its correlation with disease severity. Vet Dermatol. 2016 Feb;27(1):26-9. https://doi.org/10.1111/vde.12279
 
Ito Y, Adachi Y, Makino T, Higashiyama H, Fuchizawa T, Shimizu T, Miyawaki T. Expansion of FOXP3-positive CD4+CD25+ T-cells associated with disease activity in atopic dermatitis. Ann Allergy Asthma Immunol. 2009 Aug;103(2):160-5. https://doi.org/10.1016/S1081-1206(10)60170-6
 
Jassies-van der Lee A, Rutten VP, Bruijn J, Willemse T, Broere F. CD4+ and CD8+ skin-associated T lymphocytes in canine atopic dermatitis produce interleukin-13, interleukin-22 and interferon-γ and contain a CD25+ FoxP3+ subset. Vet Dermatol. 2014 Oct;25(5):456-72. https://doi.org/10.1111/vde.12140
 
Keppel K, Campbell K, Zuckermann F, Greeley E, Schaeffer D, Husmann R. Quantitation of canine regulatory T cell populations, serum interleukin-10 and allergen-specific IgE concentrations in healthy control dogs and canine atopic dermatitis patients receiving allergen-specific immunotherapy. Vet Immunol Immunopathol. 2008 Jun 15;123(3-4):337-44. https://doi.org/10.1016/j.vetimm.2008.02.008
 
Knueppel A, Lange S, Sekora A, Altmann S, Freund M, Junghanss C. Phenotypic and functional characterization of freshly isolated and expanded canine regulatory T-cells. Exp Anim. 2011 Oct;60(5):471-9. https://doi.org/10.1538/expanim.60.471
 
Lesiak A, Smolewski P, Sobolewska-Sztychny D, Sysa-Jedrzejowska A, Narbutt J. The role of T-regulatory cells and Toll-like receptors 2 and 4 in atopic dermatitis. Scand J Immunol. 2012 Oct;76(4):405-10. https://doi.org/10.1111/j.1365-3083.2012.02739.x
 
Ling EM, Smith T, Nguyen XD, Pridgeon C, Dallman M, Arbery J, Carr VA, Robinson DS. Relation of CD4+ CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet. 2004 Feb 21;363(9409):608-15. https://doi.org/10.1016/S0140-6736(04)15592-X
 
Navarro C, Crastes N, Benizeau E, McGahie D. Voluntary acceptance and consumption of two oral ciclosporin formulations in dogs: two randomised, controlled studies. Ir Vet J. 2015 Feb 12;68(1):3. https://doi.org/10.1186/s13620-015-0031-8
 
Olivry T, Marsella R, Pucheu-Haston CM, Hammerberg B. Mechanism of lesion formation in canine atopic dermatitis: 2004 hypothesis. In: Hillier A, Foster AP, Kwochka KW, editors. Advances in Veterinary Dermatology, 5. Oxford, UK: Blackwell Publishing; 2005. p. 10-6.
 
Pinheiro D, Singh Y, Grant CR, Appleton RC, Sacchini F, Walker KR, Chadbourne AH, Palmer CA, Armitage-Chan E, Thompson I, Williamson L. Phenotypic and functional characterization of a CD4+ CD25high FOXP3high regulatory T-cell population in the dog. Immunology. 2011 Jan;132(1):111-22.  https://doi.org/10.1111/j.1365-2567.2010.03346.x
 
Takahata Y, Nomura A, Takada H, Ohga S, Furuno K, Hikino S, Nakayama H, Sakaguchi S, Hara T. CD25+ CD4+ T-cells in human cord blood: an immunoregulatory subset with naive phenotype and specific expression of forkhead box p3 (Foxp3) gene. Exp Hematol. 2004 Jul;32(7):622-9. https://doi.org/10.1016/j.exphem.2004.03.012
 
download PDF

© 2020 Czech Academy of Agricultural Sciences