mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2019-6-1023-1032mimmun-1766Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESСтруктурно-функциональная характеристика субпопуляции Т-хелперов 17 при аллергических заболеваниях органов дыхания у детейStructural and functional characteristics of the T helpers 17 subpopulation in allergic diseases of the respiratory organs in childrenПросековаЕ. В.ProsekovaE. V.

Просекова Елена Викторовна — доктор медицинских наук, профессор, заведующая кафедрой клинической лабораторной диагностики, общей и клинической иммунологии.

PhD, MD (Medicine), Professor, Head, Department of Clinical Laboratory Diagnostics and General and Clinical Immunology.

690002, Vladivostok, Ostryakov ave., 2. Phone/Fax: 7(423) 242-97-78

pros.ev@mail.ruhttps://orcid.org/0000-0002-8701-7213ПлеховаН. Г.PlekhovaN. G.

Плехова Наталья Геннадьевна — доктор биологических наук, заведующая центральной научноисследовательской лабораторией, профессор кафедры клинической лабораторной диагностики, общей и клинической иммунологии.

690002, Владивосток, пр. Острякова, 2,  Тел./факс: 8(423) 242-97-78

Plekhova Natalia G. - PhD, MD (Biology), Head, Central Scientific Research Laboratory, Professor, Department of Clinical Laboratory Diagnostics and General and Clinical Immunology.

Vladivostok

pl_nat@hotmail.comТурянскаяА. И.TuryanskayaA. I.

Турянская Алина Ивановна — ассистент кафедры клинической лабораторной диагностики, общей и клинической иммунологии, аспирант.

Владивосток

Assistant Professor, Department of Clinical Laboratory Diagnostics and General and Clinical Immunology, Postgraduate Student.

alinakld@mail.ruСабынычВиталий АлександровичSabynychV. A.

Сабыныч Виталий Александрович — кандидат медицинских наук, доцент кафедры клинической лабораторной диагностики, общей и клинической иммунологии.

Владивосток

PhD (Medicine), Associate Professor, Department of Clinical Laboratory Diagnostics and General and Clinical Immunology.

Vladivostok

irinidi@mail.ruФГБОУ ВО «Тихоокеанский государственный медицинский университет» Минздрава РоссииРоссияPacific State Medical UniversityRussian FederationФГБОУ ВО Тихоокеанский государственный медицинский университет Минздрава РоссииРоссияPacific State Medical UniversityRussian Federation20191001202021610231032Copyright © Просекова Е.В., Плехова Н.Г., Турянская А.И., Сабыныч В.А., 20202020Просекова Е.В., Плехова Н.Г., Турянская А.И., Сабыныч В.А.Prosekova E.V., Plekhova N.G., Turyanskaya A.I., Sabynych V.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1766

Фенотипы бронхиальной астмы и аллергического ринита разделяются в зависимости от преобладающего направления иммунного ответа по профилю Т-лимфоцитов и спектру цитокинов, регулирующих субпопуляции Т-лимфоцитов хелперов. Актуальными являются исследования патогенетических механизмов различных фенотипов аллергических заболеваний дыхательных путей и оценка структурно-функциональных характеристик ТЫ7-лимфоцитов и интерлейкина-17.

Цель исследования — провести анализ субпопуляций ТЫ7-лимфоцитов и интерлейкинов-17А, 17F при атопической бронхиальной астме и аллергическом рините у детей.

Проведена комплексная оценка структурно-функциональных характеристик Т-хелперов 17 у 60 детей в возрасте 3-11 лет с верифицированным диагнозом «атопическая бронхиальная астма» (у 44 (73,33%) детей БА сочеталась с аллергическим ринитом) и 30 здоровых сверстников, составивших группу контроля. Популяционный и субпопуляционный состав лимфоцитов крови оценивали методом проточной цитофлуориметрии с использованием моноклональных антител к CD3, CD4, CD8, CD19, CD45RA, CD45RO и CD196. Для определения внутриклеточного содержания IL-17 использовали моноклональные антитела против IL-17A (клон REA1063), меченные PE-Vio770, изотипический контроль антитела против REA (Miltenyi Biotec GmbH, Германия). Методом твердофазного иммуноферментного анализа в сыворотке крови определяли содержание общего, специфического IgE и интерлейкинов-17А и 17F. Статистическую обработку результатов проводили с использованием прикладных программ Statistica 10.

Исследования функциональных и количественных характеристик иммунокомпетентных клеток у детей с атопической бронхиальной астмой и аллергическим ринитом выявили вариативность относительного и абсолютного количества субпопуляций CD3+CD4"CD8+, CD3+CD8+CD45RA+ и CD3+CD4+CD45RA+CD45RО"Т-лимфоцитов в периферической крови без значимых различий по отношению к показателям для здоровых сверстников (р < 0,001). Значимое повышение количества Т-лимфоцитов у детей с атопической бронхиальной астмой было обнаружено в отношении субпопуляции CD3+CD8+CD45RA_CD45RO+ (р < 0,001), дифференцированной популяции CD3CD4- позитивных Т-хелперов (р < 0,05) и субпопуляции Th-эффекторов, экспрессирующих обе изоформы рецептора CD45RA и CD45RO (р < 0,01). У детей с сочетанием атопической бронхиальной астмой и аллергического ринита удельный вес CD4CD45RO-позитивных клеток памяти был ниже (р < 0,001), а количество CD8+CD45RO+T-лимфоцитов, напротив, выше (р < 0,025), чем в группе здоровых сверстников.

Phenotypes of asthma and allergic rhinitis are classified depending on the prevailing direction of the immune response the T lymphocyte profile and spectrum of cytokines that regulate the subpopulations of T lymphocyte helper cells. Therefore, the studies on the pathogenesis in various phenotypes of allergic respiratory diseases, and assessment of structural and functional characteristics of Th17 lymphocytes and interleukin 17 are relevant. The purpose of the present study was to analyze the subpopulations of Th17 lymphocytes and IL-17A, IL-17F interleukins in children with atopic asthma and allergic rhinitis. Materials and methods: a comprehensive assessment of structural and functional characteristics of T helper cells was carried out in 60 children aged 3-11 years with a verified diagnosis of atopic asthma. In 44 children (73.33% of total) bronchial asthma was combined with allergic rhinitis, and 30 healthy peers formed the control group. The population and subpopulation composition of blood lymphocytes was assessed by flow cytofluorimetry using monoclonal antibodies to CD3, CD4, CD8, CD19, CD45RA, CD45RO and CD196. To determine the intracellular content of IL-17, monoclonal antibodies against IL-17A (clone REA1063) labeled with PE-Vio770, isotypic control of antibodies against REA (Miltenyi Biotec GmbH, Germany) were used. The contents of total, specific IgE and interleukins IL-17A and IL-17F were determined by the enzyme-linked immunosorbent assay in the blood serum. Statistical processing of the results was performed using the “Statistica 10” applied software. When studying functional and quantitative characteristics of immunocompetent cells in children with atopic bronchial asthma and allergic rhinitis, a sufficient variability was revealed for relative and absolute numbers of CD3+CD4-CD8+, CD3+CD8+CD45RA+ and CD3+CD4+CD45RA+CD45RO"T lymphocyte subpopulations in peripheral blood, without significant differences with appropriate parameters in healthy controls (p < 0.001). A significant increase in the number of T lymphocytes was found in children with atopic bronchial asthma, with respect to CD3+CD8+CD45RA"CD45RO+ subpopulation (p < 0.001), the differentiated population of CD3CD4 positive T helpers (p < 0.05), and the Th effector subpopulations expressing both isoforms of CD45RA and CD45RO receptor (p < 0.01). The proportion of CD4CD45RO positive memory cells in children with atopic bronchial asthma and allergic rhinitis proved to be lower (p < 0.001), and the number of CD8+CD45RO+T lymphocytes, on the contrary, was higher (p < 0.025) than in the group of healthy controls. A diagnostically significant increase in the absolute and relative amounts of T helper 17 type with detectable changes in their functional characteristics, i.e., by the CCR6 chemokine receptor (CD196) expression levels, and presence of IL17A interleukin in children with atopic asthma and allergic rhinitis. The contents of this T helper 17 type subpopulation, and concentration of interleukins IL-17A, IL-17F in the blood serum of children with atopic asthma and allergic rhinitis showed the variability of functional and quantitative characteristics of cells that depended on the prevalence of allergic inflammation, evident imbalance in the interleukin 17 system, and the influence of Th17 lymphocytes on various aspects of inflammation and bronchial hyperreactivity associated with Th1 and Th2 response.

Т-хелперы 17интерлейкин-17Аттерлейкт-nFаллергический ринитатопическая бронхиальная астмадетиThelper 1717A17F interleukinsallergic rhinitisatopic bronchial asthmachildrenReferencesКайдашев И.П. Т-клеточная регуляция при атопических заболеваниях // Клиническая иммунология. Аллергология. Инфектология, 2011. № 9-10. С. 18-21.Kaydashev I.P. T cell regulation in atopic diseases. Klinicheskaya immunologiya. Allergologiya. Infektologiya = Clinical Immunology. Allergology. Infectology, 2011, no. 9-10, pp. 18-21. (In Russ.)Кудрявцев И.В., Борисов А.Г., Волков А.Е., Савченко А.А., Серебрякова М.К., Полевщиков А.В. Анализ уровня экспрессии CD56 и CD57 цитотоксическими Т-лимфоцитами различного уровня диффе-ренцировки // Тихоокеанский медицинский журнал, 2015. № 2. С. 30-35.Kudryavtsev I.V., Borisov A.G., Volkov A.E., Savchenko A.A., Serebryakova M.K., Polevshchikov A.V. Analysis of the expression level of CD56 and CD57 by cytotoxic T lymphocytes of different levels of differentiation. Tikhookeanskiy meditsinskiy zhurnal = Pacific Medical Journal, 2015, no. 2, pp. 30-35. (In Russ.)Курбачева О.М., Жестков А.В., Нагаткин Д.А., Кулагина В.В., Нагаткина О.В. Современный взгляд на иммунопатогенез бронхиальной астмы // Российский аллергологический журнал, 2016. № 2. С. 10-14.Kurbacheva O.M., Zhestkov A.V., Nagatkin D.A., Kulagina V.V., Nagatkina O.V. Modern view on the immunopathogenesis of bronchial asthma. Rossiyskiy allergologicheskiy zhurnal = Russian Allergology Journal, 2016, no. 2, pp. 10-14. (In Russ.)Нурдина М.С., Купаев В.И. Взаимосвязь уровня IL-17, IL-10 со степенью контроля бронхиальной астмы // Вестник современной клинической медицины, 2017. Т. 10, № 3. С. 35-38.Nurdina M.S., Kupaev VI. The relationship of the level of IL-17, IL-10 with the degree of control of asthma. Vestnik sovremennoy klinicheskoy meditsiny = Journal of Modern Clinical Medicine, 2017, Vol. 10, no. 3, pp. 35-38. (In Russ.)Симбирцев А.С. Цитокины в патогенезе и лечении заболеваний человека. М.: Фолиант, 2018. 512 с.Simbirtsev A.S. Cytokines in the pathogenesis and treatment of human diseases]. Moscow: Foliant, 2018. 512 p.Хайдуков С.В., Байдун Л.В., Зурочка А.В., Тотолян Арег А. Стандартизованная технология «Исследование субпопуляционного состава лимфоцитов периферической крови с применением проточных цитофлюориметров-анализаторов» // Российский иммунологический журнал, 2014. Т. 8, № 4. С. 974-992.Khaydukov S.V., Baydun L.A., Zurochka A.V., Totolyan A.A. The standardized technique “Study subpopulations of peripheral blood lymphocytes by using flow cytometry” Russian Journal of Immunology, 2014, Vol. 8, no. 4, pp. 974-992. (In Russ.)Acosta-Rodriguez E.V, Napolitani G., Lanzavecchia A., Sallusto F. Interleukins 1 p and 6 but not transforming growth factor-P are essential for the differentiation оf interleukin 17-producing human T helper cells. Nat. Immunol., 2007, Vol. 8, no. 9, pp. 942-949.Acosta-Rodriguez E.V, Napolitani G., Lanzavecchia A., Sallusto F. Interleukins 1 p and 6 but not transforming growth factor-P are essential for the differentiation оf interleukin 17-producing human T helper cells. Nat. Immunol., 2007, Vol. 8, no. 9, pp. 942-949.Agache С., Akdis C., Jutel M., Virchov J.S. Untangling asthma phenotypes and endotypes. Allergy, 2012, Vol. 67, pp. 835-846.Agache С., Akdis C., Jutel M., Virchov J.S. Untangling asthma phenotypes and endotypes. Allergy, 2012, Vol. 67, pp. 835-846.Agache I., Ciobanu C., Agache C., Anghel M. Increased serum IL-17 is an independent risk factor for severe asthma. Respiratory Med., 2010, Vol. 104, pp. 1131-1137.Agache I., Ciobanu C., Agache C., Anghel M. Increased serum IL-17 is an independent risk factor for severe asthma. Respiratory Med., 2010, Vol. 104, pp. 1131-1137.Akdis C.A. Global atlas of asthma. Switzerland: Published by the European Academy of Allergy and Clinical Immunology (ed.: Akdis C.A., Agache I.), 2013, pp. 2-179.Akdis C.A. Global atlas of asthma. Switzerland: Published by the European Academy of Allergy and Clinical Immunology (ed.: Akdis C.A., Agache I.), 2013, pp. 2-179.Akdis M. The pathogenesis of astma. Global atlas of Asthma, 2013, pp. 28-30.Akdis M. The pathogenesis of astma. Global atlas of Asthma, 2013, pp. 28-30.Bacharier L.B., Boner A., Carlsen K.-H., Eigenmann P.A., Frischer T., G5tz M., Helms P. J., Hunt J., Liu A., Papadopoulos N., Platts-Mills T., Pohunek P., Simons F.E.R., Valovirta E., Wahn U., Wildhaber J., The European Pediatric Asthma Group. Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report. Allergy, 2008, Vol. 63, pp. 5-34.Bacharier L.B., Boner A., Carlsen K.-H., Eigenmann P.A., Frischer T., G5tz M., Helms P. J., Hunt J., Liu A., Papadopoulos N., Platts-Mills T., Pohunek P., Simons F.E.R., Valovirta E., Wahn U., Wildhaber J., The European Pediatric Asthma Group. Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report. Allergy, 2008, Vol. 63, pp. 5-34.Bhakta N.R. IL-17 and “TH2-high” asthma: Adding fuel to the fire? J. Allergy Clin. Immunol., 2014, Vol. 134, pp. 1187-1188.Bhakta N.R. IL-17 and “TH2-high” asthma: Adding fuel to the fire? J. Allergy Clin. Immunol., 2014, Vol. 134, pp. 1187-1188.Bossowski A., Moniuszko M., Idzkowska E., D^browska M., Jeznach M., Sawicka B., Borysewicz-Sanczyk H., Bossowska A., Rusak M., Bodzenta, Lukaszyk A. Evaluation of CD4+CD161+CD196+ and CD4+IL-17+ Th17 cells in the peripheral blood of young patients with Hashimoto’s thyroiditis and Graves’ disease. Pediatr. Endocrinol. Diabetes Metab., 2012, Vol. 18, no. 3, pp. 89-95.Bossowski A., Moniuszko M., Idzkowska E., D^browska M., Jeznach M., Sawicka B., Borysewicz-Sanczyk H., Bossowska A., Rusak M., Bodzenta, Lukaszyk A. Evaluation of CD4+CD161+CD196+ and CD4+IL-17+ Th17 cells in the peripheral blood of young patients with Hashimoto’s thyroiditis and Graves’ disease. Pediatr. Endocrinol. Diabetes Metab., 2012, Vol. 18, no. 3, pp. 89-95.Bousquet J., Pfaar O., Togias A. et al. Allergic Rhinitis and its Impact on Asthma (ARIA) Care pathways for allergen immunotherapy. Allergy, 2019, Vol. 74, no. 11, pp. 2087-2102.Bousquet J., Pfaar O., Togias A. et al. Allergic Rhinitis and its Impact on Asthma (ARIA) Care pathways for allergen immunotherapy. Allergy, 2019, Vol. 74, no. 11, pp. 2087-2102.Cosmi L., Liotta F., Maggi E., Romagnani S., Annunziato F. Th17-cells: new players in asthma pathogenesis. Allergy, 2011, Vol. 66, pp. 989-998.Cosmi L., Liotta F., Maggi E., Romagnani S., Annunziato F. Th17-cells: new players in asthma pathogenesis. Allergy, 2011, Vol. 66, pp. 989-998.Dehzad N., Bopp T., Reuter S., Klein M., Martin H., Ulges A., Stassen M., Schild H., Buhl R., Schmitt E., Taube C. Regulatory T-cells more effectively suppress Th1-incluced airway inflammation compared with Th2. J. Immunol., 2011, Vol. 186, pp. 238-244.Dehzad N., Bopp T., Reuter S., Klein M., Martin H., Ulges A., Stassen M., Schild H., Buhl R., Schmitt E., Taube C. Regulatory T-cells more effectively suppress Th1-incluced airway inflammation compared with Th2. J. Immunol., 2011, Vol. 186, pp. 238-244.Doe C., Bafahel M., Siddiqui S., Desai D., Mistry V., Rugman P., McCormick M., Woods J., May R., Sleeman M.A., Anderson I.K., Brightling C.E. Expression of the T helper 17-associated cytokines IL-17A and IL-17F in asthma and COPD. CHEST, 2010, Vol. 138, no. 5, pp. 1140-1147.Doe C., Bafahel M., Siddiqui S., Desai D., Mistry V., Rugman P., McCormick M., Woods J., May R., Sleeman M.A., Anderson I.K., Brightling C.E. Expression of the T helper 17-associated cytokines IL-17A and IL-17F in asthma and COPD. CHEST, 2010, Vol. 138, no. 5, pp. 1140-1147.Francis J.N., Sabroe I., Lloyd C.M., Durham S.R., Till S.J. Elevated CCR6+ CD4+ T lymphocytes in tissue compared with blood and induction of CCL20 during the asthmatic late response. Clin. Exp. Immunol., 2008, Vol. 152, no. 3, pp. 440-447.Francis J.N., Sabroe I., Lloyd C.M., Durham S.R., Till S.J. Elevated CCR6+ CD4+ T lymphocytes in tissue compared with blood and induction of CCL20 during the asthmatic late response. Clin. Exp. Immunol., 2008, Vol. 152, no. 3, pp. 440-447.Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2018. Available from: ginasthma.org.Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2018. Available from: ginasthma.org.Hayashida S., Uchi H., Moroi Y., Furue M. Decrease in circulating Th17 cells correlates with increased levels of CCL17, IgE and eosinophils in atopic dermatitis. J. Dermatol. Sci., 2011, Vol. 61, no. 3, pp. 180-186.Hayashida S., Uchi H., Moroi Y., Furue M. Decrease in circulating Th17 cells correlates with increased levels of CCL17, IgE and eosinophils in atopic dermatitis. J. Dermatol. Sci., 2011, Vol. 61, no. 3, pp. 180-186.Kerzel S., Dehne J., Rogosch T., Schaub B., Maier R.F., Zemlin M. Th17 cell frequency in peripheral blood from children with allergic asthma correlates with the level of asthma control. J. Pediatr., 2012, Vol. 61, no. 6, pp. 1172-1174.Kerzel S., Dehne J., Rogosch T., Schaub B., Maier R.F., Zemlin M. Th17 cell frequency in peripheral blood from children with allergic asthma correlates with the level of asthma control. J. Pediatr., 2012, Vol. 61, no. 6, pp. 1172-1174.Kimura A., Kishimoto T. IL 6: regulator of Treg/Th17 balance. Eur. J. Immunol., 2010, Vol. 40, no. 7, pp. 1830-1835.Kimura A., Kishimoto T. IL 6: regulator of Treg/Th17 balance. Eur. J. Immunol., 2010, Vol. 40, no. 7, pp. 1830-1835.Koch S., Sopel N., Finotto S. Th9 and other IL-9-producing cells in allergic asthma. Semin. Immunopathol., 2017, Vol. 3, no. 1, pp. 55-68.Koch S., Sopel N., Finotto S. Th9 and other IL-9-producing cells in allergic asthma. Semin. Immunopathol., 2017, Vol. 3, no. 1, pp. 55-68.Mahnke Y.D., Roederer M. Optimizing a multicolor immunophenotyping assay. Clin. Lab. Med., 2007, Vol. 27, no. 3, pp. 469-485.Mahnke Y.D., Roederer M. Optimizing a multicolor immunophenotyping assay. Clin. Lab. Med., 2007, Vol. 27, no. 3, pp. 469-485.McKinley L., Alcorn J.F., Peterson A., Dupont R.B., Kapadia S., Logar A., Henry A., Irvin C.G., Piganelli J.D., Ray A., Kolls J.K. TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice. J. Immunol., 2008, Vol. 181, no. 6, pp. 4089-4097.McKinley L., Alcorn J.F., Peterson A., Dupont R.B., Kapadia S., Logar A., Henry A., Irvin C.G., Piganelli J.D., Ray A., Kolls J.K. TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice. J. Immunol., 2008, Vol. 181, no. 6, pp. 4089-4097.Muehling L.M., Lawrence M.G., Woodfolk J.A. Pathogenic CD4+ T cells in patients with asthma. J. Allergy Clin. Immunol., 2017, Vol. 140, no. 6, pp. 1523-1540.Muehling L.M., Lawrence M.G., Woodfolk J.A. Pathogenic CD4+ T cells in patients with asthma. J. Allergy Clin. Immunol., 2017, Vol. 140, no. 6, pp. 1523-1540.Nakae S., Iwakura Y., Suto H., Galli S.J. Phenotypic differences between Th1 and Th17 cells and negative regulation by Th17. J. Leukoc. Biol., 2007, Vol. 81, pp. 1258-1268.Nakae S., Iwakura Y., Suto H., Galli S.J. Phenotypic differences between Th1 and Th17 cells and negative regulation by Th17. J. Leukoc. Biol., 2007, Vol. 81, pp. 1258-1268.Nieminen K., Valovirta E., Savolainen J. Clinical outcome and IL-17, IL23, IL-27 and FOXP3 expression in peripheral blood mononuclear cells of pollen-allergic children during sublingual immunotherapy. Pediatr. Allergy Immunol., 2010, Vol. 21, pp. e174-e184.Nieminen K., Valovirta E., Savolainen J. Clinical outcome and IL-17, IL23, IL-27 and FOXP3 expression in peripheral blood mononuclear cells of pollen-allergic children during sublingual immunotherapy. Pediatr. Allergy Immunol., 2010, Vol. 21, pp. e174-e184.Qian Y., Kang Z., Liu C., Li X. IL-17 signaling in host defense and inflammatory diseases. Cell. Mol. Immunol., 2010, Vol. 7, no. 5, pp. 328-333.Qian Y., Kang Z., Liu C., Li X. IL-17 signaling in host defense and inflammatory diseases. Cell. Mol. Immunol., 2010, Vol. 7, no. 5, pp. 328-333.Qu N., Xu M., Mizoguchi I., Furusawa J., Kaneko K., Watanabe K., Mizuguchi J., Itoh M., Kawakami Y., Yoshimoto T. Pivotal roles of T-helper 17-related cytokines, IL-17, IL-22, and IL-23, in inflammatory diseases. Clin. Dev. Immunol, 2013, Vol. 2013, 968549. doi: 10.1155/2013/968549.Qu N., Xu M., Mizoguchi I., Furusawa J., Kaneko K., Watanabe K., Mizuguchi J., Itoh M., Kawakami Y., Yoshimoto T. Pivotal roles of T-helper 17-related cytokines, IL-17, IL-22, and IL-23, in inflammatory diseases. Clin. Dev. Immunol, 2013, Vol. 2013, 968549. doi: 10.1155/2013/968549.Seoung J.P., Lee Y.C. Interleukin-17 regulation: an attractive therapeutic approach for asthma. Respir. Res., 2010, Vol. 11, no. 1, p. 78.Seoung J.P., Lee Y.C. Interleukin-17 regulation: an attractive therapeutic approach for asthma. Respir. Res., 2010, Vol. 11, no. 1, p. 78.Singh S.P., Zhang H.H., Foley J.F., Hedrick M.N., Farber J.M. Human T cells that are able to produce IL-17 express the chemokine receptor CCR6. J. Immunol., 2008, Vol. 180, no. 1, pp. 214-221.Singh S.P., Zhang H.H., Foley J.F., Hedrick M.N., Farber J.M. Human T cells that are able to produce IL-17 express the chemokine receptor CCR6. J. Immunol., 2008, Vol. 180, no. 1, pp. 214-221.Sundrud M.S., Trivigno C. Identity crisis of Th17 cells: many forms, many functions, many questions. Semin. Immunol., 2013, Vol. 25, no. 4, pp. 263-272.Sundrud M.S., Trivigno C. Identity crisis of Th17 cells: many forms, many functions, many questions. Semin. Immunol., 2013, Vol. 25, no. 4, pp. 263-272.van de Veen W, Akdis M. Mechanisms of immune regulation in allergy. Global Atlas of Allergy, 2014, pp. 90-91.van de Veen W, Akdis M. Mechanisms of immune regulation in allergy. Global Atlas of Allergy, 2014, pp. 90-91.Wenzel S. Phenotypes & Endotypes: Emerging concepts on asthma heterogeneity. Global Atlas of Asthma, 2013, pp. 34-36.Wenzel S. Phenotypes & Endotypes: Emerging concepts on asthma heterogeneity. Global Atlas of Asthma, 2013, pp. 34-36.Winer R., Qin X., Harrington T., Moorman J., Zahran H. Asthma incidence among children and adults: findings from the behavioral risk factor surveillance system asthma callback survey-United States, 2006-2008. J. Asthma, 2012, Vol. 49, pp. 16-22.Winer R., Qin X., Harrington T., Moorman J., Zahran H. Asthma incidence among children and adults: findings from the behavioral risk factor surveillance system asthma callback survey-United States, 2006-2008. J. Asthma, 2012, Vol. 49, pp. 16-22.Zhao Y., Yang J., Gao Y.D., Guo W. Th17 immunity in patients with allergic asthma. Int. Arch. Allergy Immunol., 2010, Vol. 151, pp. 297-307.Zhao Y., Yang J., Gao Y.D., Guo W. Th17 immunity in patients with allergic asthma. Int. Arch. Allergy Immunol., 2010, Vol. 151, pp. 297-307.

The authors declare that there are no conflicts of interest present.