Russian Journal of AllergyRussian Journal of AllergyРоссийский Аллергологический Журнал1810-88302686-682XPublishing House ABV Press46910.36691/RJA469ArticlesСтатьиReview ArticleCharacteristics of immune response and role of cytokines in atopic dermatitisОсобенности иммунного ответа и роль некоторых цитокинов при атопическом дерматитеElisyutinaO GЕлисютинаО Гel-olga@yandex.ruFedenkoE SФеденкоЕ СBoldyrevaM NБолдыреваМ НGudimaG OГудимаГ ОInstitute of ImmunologyФГБУ «ГНЦ институт иммунологии» ФМБА России15022015121NO1 (2015)№1 (2015)31410032020Copyright ©; 2015, Pharmarus Print MediaCopyright ©; 2015, Фармарус Принт Медиа2015Pharmarus Print MediaФармарус Принт Медиаhttps://rusalljournal.ru/raj/article/view/469

AD is a multifactorial disease, which is based on genetic disorders, immune mechanisms and influence of exogenous and endogenous factors. Study of immunopathogenesis of atopic dermatitis, it’s specific biomarkers, triggers is very important for understanding of causes and mechanisms of the disease as well as for developing of new methods of treatment. The review describes the current views on the immune response in AD.

Атопический дерматит (АтД) относится к многофакторным заболеваниям, в основе которого лежат генетические нарушения, сложные иммунные механизмы развития и влияние комплекса экзогенных и эндогенных факторов. изучение особенностей иммунопатогенеза АтД, роли определенных биомаркеров, триггерных факторов является крайне важным не только для понимания причин и механизмов развития болезни, но и в связи с необходимостью разработки новых методов лечения. В обзоре освещены современные взгляды на иммунный ответ при АтД.

atopic dermatitisimmunopathogenesiscytokinesатопический дерматитиммунопатогенезцитокиныАллергология и иммунология: национальное руководство. Под ред. Р.М. Хаитова, Н.И. Ильиной. М., «Гэотар-Медиа». 2009, 656 с.Bieber T. Atopic dermatitis 2.0: From the clinical phenotype to the molecular taxonomy and stratified medicine. Allergy. 2012, v. 67, p. 1475-1482.Asher M.I., Montefort S., Bjorksten B. et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: isaac phases one and three repeat multicountry cross-sectional surveys. Lancet. 2006, v. 368, p. 733-743.Ring J., Alomar A., Bieber T. et al. Guidelines for treatment of atopic eczema (atopic dermatitis). Part I. J. Eur. Acad. Dermatol. Venereol. 2012, v. 26, ps. 1045-1060.Ring J., Alomar A., Bieber T et al. Guidelines for treatment of atopic eczema (atopic dermatitis). Part II. j. Eur. Acad. Dermatol. Venereol. 2012, v. 26, p. 1176-1193.Белова О.В., Арион В.Я. Иммунологическая функция кожи и нейроиммунокожная система. Аллергология и иммунология. 2006, № 7, c. 492-497.Schauber J., Gallo R.L. Antimicrobial peptides and the skin immune defense system. j. Allergy Clin. Immunol. 2008, v. 122, p. 261-266.Bieber T. Mechanisms of disease atopic dermatitis. N. Engl. J. Med. 2008, v. 358, p. 1483-1494.Leung D.Y., Bieber T. Atopic dermatitis. Lancet. 2003, v. 361, p. 151-160.Steinhoff M., Bienenstock J., Schmelz M. Neurophysiological, neuroimmunological and neuroendocrine basis of pruritus. J. Invest. Dermatol. 2006, v. 126, p. 1705-1718.Leung D. Pathogenesis of atopic dermatitis. J. Allergy Clin. Immunol. 1999, v. 104, p. 99-108.Williams H., Flohr C. How epidemiology has challenged 3 prevailing concepts about atopic dermatitis. J. Allergy Clin. Immunol. 2006, v. 118, p. 209-213.Illi S., Von mutius E., Lau S. et al. The natural course of atopic dermatitis from birth to age 7 years and the association with asthma. j. Allergy Clin. Immunol. 2004, v. 113, p. 925-931.Elias P.M., Menon G.K. Structural and lipid biochemical correlates of the epidermial permeability barrier. In: Skin Lipids, Advances in Lipid Research. San Diego, Academic Press Inc. 1991, p. 26.Proksch E., Fölster-holst R., Jensen J.M. Skin barrier function, epidermal proliferation and differentiation in eczema. J. Dermatol. Sci. 2006, v. 43, p159-169.Гущин И.С. Эпидермальный барьер и аллергия. Рос. Аллергол. Журн. 2007, № 2, c. 3-16.Cork M.J., Danby S.G., Vasilopoulos Y. et al. Epidermal barrier dysfunction in atopic dermatitis. j. Invest. Dermatol. 2009, v. 129, p. 1892-1908.Scharschmidt T.C., Man M.Q., Hatano Y. et al. Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens. J. Allergy Clin. Immunol. 2009, v. 124, p. 496-506.Elias P.M., Eichenfield L.F., Fowler J.F. et al. Update on the structure and function of the skin barrier: atopic dermatitis as an exemplar of clinical implications. Semin. Cutan. Med. Surg. 2013, v. 32, p. 21-24.Brown S.J., Relton C.L., Liao H. et al. Filaggrin null mutations and childhood atopic eczema: a population-based case-control study, j. Allergy Clin. Immunol. 2008, v. 121, p. 940-946.Irvine A.D., Mclean W.H., Leung D.Y Filaggrin mutations associated with skin and allergic diseases. N. Engl. J. Med. 2011, v. 365, p. 1315-1327.Lee Y., Wahn U. Genetic dissection of eczema. In: Reitamo S., Luger T.M., Steinhof M. Eds. Textbook of atopic dermatitis, informa UK Ltd. 2008, p. 13-24.Hwang S.T. Mechanisms of T-cell homing to skin. Adv. Dermatol. 2001, v. 17, p. 211-241.Grewe M., Gyufko K., Schopf E. et al. Lesional expression of interferon gamma in atopic eczema. Lancet. 1994, v. 343, p. 25-26.Wistokat-Wulfing A., Schmidt P., Darsow U. et al. Atopy patch test reactions are associated with T-lymphocyte - mediated allergen specific responses in atopic dermatitis. Clin. Exp. Allergy. 1999, v. 29, p. 513-521.Novak N., Valenta R., Bohle B. et al. FεRI engagement of Langerhans cell-like dendritic cells and inflammatory dendritic epidermal cell-like dendritic cells induces chemotactic signals and different T-cell phenotypes in vitro. j. Allergy Clin. Immunol. 2004, v. 113, p. 949-957.Mudde G.C., Van reijsen F.C., Boland G.J. et al. Allergen presentation by epidermal langerhans cells from patients with atopic dermatitis is mediated by IgE. Immunol. 1990, v. 69, p. 41-335.Soumelis V., Reche P.A., Kanzler H. et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat. Immunol. 2002, v. 3, p. 673-680.Bratton D.L., Hamid Q., Boguniewicz M. et al. Granulocyte macrophage colony-stimulating factor contributes to enhanced monocyte survival in chronic atopic dermatitis. j. Clin. Invest. 1995, v. 95, p. 211-218.Bieber T. Mechanisms of disease atopic dermatitis. N. Engl. j. Med. 2008, v. 35, p. 1483-1494.Souwer Y., Szegedi K., Kapsenberg M.L., De joing E.C. IL-17 and IL-22 in atopic allergic deseases. Curr. Opin. Immunol. 2010, v. 22, p. 821-826.Korn T., Betelli E., Oukka M., Kuchroo VK. IL-17 and Th17-cells. Ann. Rev. Immunol. 2009, v. 27, p. 485-517.Wolk K., Kunz S., Witte E. et al. IL-22 increases the innate immunity of tissues. Immunity. 2004, v. 21, p. 241-254.Novak N., Bieber T. The role of dendritic cell subtypes in the pathophysiology of atopic dermatitis. j. Am. Acad. Dermatol. 2005, v. 5, p. 171-176.Wollenberg A., Wagner M., Gunther S. et al. Plasmacytoid dendritic cells: a newcutaneous dendritic cell subset with distinct role in inflammatory skin diseases. j. Invest. Dermatol. 2002, v. 119, p. 1096-1102.Wollenberg A., Kraft S., Hanau D., Bieber T. Immunomorphological and ultrastructural characterization of langerhans cells and a novel, inflammatory dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema. J. Invest. Dermatol. 1996, v. 106, p. 446-453.Bieber T. The pro- and anti-inflammatory properties of human antigen-presenting cells expressing the high affinity receptor for IgE (FcεRI). Immunobiology. 2007, v. 212, p. 499-503.Reich K., Heine A., Hugo S. et al. Engagement of the FcεRI stimulates the production of IL-16 in langerhans cell-like dendritic cells. j. Immunol. 2001,v. 167, p. 6321-6329.Kerschenlohr K., Decard S., Przybilla B., Wollenberg A. Atopy patch test reactions show a rapid influx of inflammatory dendritic epidermal cells in patients with extrinsic atopic dermatitis and patients with intrinsic atopic dermatitis. j. Allergy Clin. Immunol. 2003, v. 111, p. 869-874.Gantner F., Gotz C., Gekeler V. et al. Phosphodiesterase profile of human B-lymphocytes from normal and atopic donors and the effects of pde inhibition on B-cell proliferation. Br. j. Pharmacol. 1998, v. 123, p. 1031-1038.Novak N., Allam P., Geiger E. et al. Characterization of monocyte subtypes in the allergic form of atopic eczema/dermatitis syndrome. Allergy. 2002, v. 57, p. 931-935.Heinisch I.V., Bizer C., Volgger W. et al. Functional CD137 receptors are expressed by eosinophils from patients with IgE-mediated allergic responses but not by eosinophils from patients with non-IgE-mediated eosinophilic disorders. J. Allergy Clin. Immunol. 2001, v. 108, p. 21-28.Taha R.A., Minshall E.M., Leung D.Y. et al. Evidence for increased expression of eotaxin and monocyte chemotactic protein-4 in atopic dermatitis. j. Allergy Clin. Immunol. 2000, v. 105, p. 1002-1007.Kay A.B., Barata L., Meng Q. et al. Eosinophils and eosinophil-associated cytokines in allergic inflammation. Int. Arch. Allergy Immunol. 1997, v. 113, p. 196-199.Pastore S., Mascia F., Girolomoni G. The contribution of keratinocytes to the pathogenesis of atopic dermatitis. Eur. J. Dermatol. 2006, v. 16, p. 125-131.Morales J., Homey B., Vicari A.P. et al. Ctack, a skin-associated chemokine that preferentially attracts skin-homing memory T-cells. Proc. Natl. Acad. Sci. USA. 1999, v. 96, p. 14470-14475.Gombert M., Dieu-nosjean M.C., Winterberg F. et al. CCL1-CCR8 interactions: an axis mediating the recruitment of T-cells and langerhans-type dendritic cells to sites of atopic skin inflammation. j. Immunol. 2005, v. 174, p. 5082-5091.Ильина Н.И., Гудима ГО. Воспаление и иммунитет в общеклинической практике. Общая концепция. Цитокины и воспаление. 2005, № 3, c. 42-44.Akdis M., Burgler S., Crameri R. et al. Interleukins, from 1 to 37, and interferon-у: receptors, functions, and roles in diseases. J. Allergy Clin. Immunol. 2011, v. 127, p. 701-721.Белова О.В., Арион В.Я., Сергиенко В.И. Роль цитокинов в иммунологической функции кожи. Иммунология, аллергология, инфектология. 2008, № 1, c. 41-55.Schmitt J., Schmitt N., Meurer M. Cyclosporin in treatment of patients with atopic dermatitis - a systematic review and metaanalysis. j. Eur. Acad. Dermatol. Veneorol. 2007, v. 21, p. 606-619.Hon K.L., Ching G.K., Leung T.F. Efficacy and tolerability at 3 and 6 months following use of azathioprine for recalcitrant atopic dermatitis in children and young adults. J. Dermatolog. Treat. 2009, v. 20, p. 141-145.Murray M.L., Cohen J.B. Mycophenolate mofetil therapy for moderate to severe atopic dermatitis. Clin. Exp. Dermatol. 2007, v. 32, p. 23-27.Breedveld F.C. Therapeutic monoclonal antibodies. Lancet. 2000, v. 355, p. 735-740.Antoniu S.A. Pitrakinra, a dual IL-4/IL-13 antagonist for the potential treatment of asthma and eczema. Curr. Opin. Investig. Drugs. 2010, v. 11, p. 1286-1294.Sheinkopf L.E., Rafi A.W., Do L.T. et al. Efficacy of omalizumab in the treatment of atopic dermatitis: a pilot study. Allergy asthma proc. 2008, v. 29, p. 530-537.Belloni B., Ziai M., Lim A. et al. Low-dose anti-IgE therapy in patients with atopic eczema with high serum IgE levels. J. Allergy Clin. Immunol. 2007, v. 120, p. 1223-1225.Kasperkiewicz M., Schmidt E., Frambach Y. et al. Improvement of treatment-refractory atopic dermatitis by immunoadsorption: a pilot study. J. Allergy Clin. Immunol. 2011, v. 127, p. 267-270.Simon D., Hosli S., Kostylina G. et al. Anti-CD20 (rituximab) treatment improves atopic eczema. J. Allergy Clin. Immunol. 2008, v. 121, p. 122-128.Sediva A., Kayserova J., Vernerova E. et al. Anti-CD20 (rituximab) treatment for atopic eczema. J. Allergy Clin. Immunol. 2008, v. 121, p. 1515-1516.Oldhoff J.M., Darsow U., Werfel T. et al. Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy. 2005, v. 60, p. 693-696.Luger T.A., Steinhoff M. Experimental therapeutic strategies for the treatment of atopic dermatitis. In: Reitamo S., Luger T.M., Steinhof M. Textbook of atopic dermatitis. Informa UK Ltd. 2008, p. 247-260.