mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-IRI-2138mimmun-2138Research ArticleОБЗОРЫREVIEWSИммунный ответ при атопическом дерматите. Основные патогенетические механизмы и корреляции стадийности в возрастном аспекте. Взаимосвязь с системными процессами дерматологического и недерматологического профиляImmune response in atopic dermatitis: main pathogenetic mechanisms and stage-dependent correlations with age in regard to dermatological and non-dermatological systemic processesДрождинаМ. Б.DrozhdinaM. B.

к.м.н., доцент, доцент кафедры дерматовенерологии и косметологии,

610998, г. Киров, ул. К. Маркса, 112

PhD (Medicine), Associate Professor, Department of Dermatovenereology and Cosmetology,

610998, Kirov, K. Marx str., 112

drozhdina@yandex.ruСусловаЕлена ВикторовнаSuslovaE. V.

 к.м.н., врач ультразвуковой диагностики,

г. Киров

PhD (Medicine), Doctor for Ultrasound Diagnostics, 

Kirov

ozon43@mail.ruФГБОУ ВО «Кировский государственный медицинский университет» Министерства здравоохранения РФРоссияKirov State Medical UniversityRussian FederationКОГБУЗ «Детский клинический консультативно-диагностический центр»РоссияPediatric Clinical Consultative and Diagnostic Center of the Kirov RegionRussian Federation202124042021232237244Copyright © Дрождина М.Б., Суслова Е.В., 20212021Дрождина М.Б., Суслова Е.В.Drozhdina M.B., Suslova E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2138

Атопический дерматит – одно из наиболее распространенных хронических воспалительных заболеваний кожи, обусловлено как терминальными дефектами дифференцировки кератиноцитов, так и выраженными иммунными реакциями 2-го типа. Атопический дерматит – достаточно гетерогенное заболевание, в зависимости от возрастного подтипа, вызванное активацией Th22-, Th17/ IL-23- и Th1-пути цитокинов. Клинические исследования с применением классической и таргетной терапии помогли выяснить вклад различных иммунных осей в фенотип заболевания.

Представлена современная теория опосредованности активации Th2-реакций за счет врожденных лимфоидных клеток 2-й группы. Описаны корреляции иммунного ответа при острых (IL-4, IL-5, IL-13, IL-31, CCL18, IL-22, белки S100A) и хронических (IFNγ, CXCL9 и CXCL10) проявлениях атопического дерматита. Обсуждается теория взаимосвязи клинических проявлений и сверхэкспрессии ряда цитокинов (IL-4, IL-13). Показана корреляция фенотипа периферической крови при атопическом дерматите раннего детского возраста и у взрослых пациентов с выработкой отдельных сывороточных биомаркеров. В дополнение к избыточной выработке Th17, раннее начало атопического дерматита у детей коррелировало с повышенными уровнями антимикробных пепдидов, что может служить сигнальным маркером, запускающим заболевание. В статье даны сведения о взаимосвязи атопического дерматита с другими системными неаллергическими процессами и заболеваниями (псориаз, атеросклероз, сердечно-сосудистые заболевания, ожирение). Несмотря на разную полярность Т-клеток при атопическом дерматите и псориазе и разные группы вырабатываемых цитокинов при данных заболеваниях (псориаз в значительной степени обусловлен Th17 и связанной с ними активацией IL-17, атопический дерматит – следствие доминирования Th2, и связанной с ними избыточной продукцией IL-4 и IL-13), оба заболевания демонстрируют активацию Th1 и Th22 с повышением продукции интерферона-γ и IL-22 соответственно. В статье также описана интересная гипотеза влияния белка TWEAK на течение атопического дерматита и псориаза. Кератиноциты и фибробласты кожи в ответ на повышенную активность TWEAK производят ряд хемоатрактивных и провоспалительных факторов, обычно встречающихся при атопическом дерматите и псориазе, в частности IL-13 и IL-17. Изолированно TWEAK не является этиологическим фактором атопического дерматита или псориаза, но он вызывает продукцию хемокинов, которые способствуют хемотаксису патогенных воспалительных клеток в кожу. При дальнейшем изучении данного патогенетического фактора станет возможным синтезировать новый таргетный препарат для лечения атопического дерматита и псориаза. 

Atopic dermatitis is one of the most common chronic inflammatory skin diseases caused by both terminal defects in keratinocyte differentiation, and pronounced type 2 immune responses. Atopic dermatitis is a fairly heterogenous disease, depending on the age subtype caused by activation of the Th22, Th17/IL-23 and Th1 cytokine pathway. Clinical studies using classical and targeted therapies have helped to determine contribution of various immune axes to the disease phenotype.

We present the modern activation theory mediated by Th2 reactions, due to congenital lymphoid cells of the 2nd group. Correlations between immune response in acute (IL-4, IL-5, IL-13, IL-31, CCL18, IL-22, S100A proteins) and chronic (IFNγ, CXCL9, and CXCL10) manifestations of atopic dermatitis are described. The theory of relationship between clinical manifestations and overexpression of some cytokines (IL-4, IL-13) is discussed. The correlation was shown between peripheral blood phenotype in atopic dermatitis of early childhood and in adult patients and individual production of serum biomarkers. In addition to excess Th17 production, early onset of atopic dermatitis in children correlated with elevated levels of antimicrobial peptides, which may serve as a signaling marker that triggers the disease. The article provides information about relationship between atopic dermatitis and other systemic non-allergic processes and diseases (psoriasis, atherosclerosis, cardiovascular diseases, obesity). Despite different polarity of T cells in atopic dermatitis and psoriasis, and different groups of cytokines produced in these diseases. Psoriasis is most of all due to Th17 associated with activation of IL-17, whereas atopic dermatitis is a consequence of Th2 dominance and associated excessive production of IL-4 and IL-13. The both diseases show activation of Th1 and Th22 with increased production of interferon-γ and IL-22, respectively. The article also concerns an interesting hypothesis on effects of the TWEAK protein upon clinical course of atopic dermatitis and psoriasis. In response to increased TWEAK activity, keratinocytes and skin fibroblasts produce a number of chemoattractant and pro-inflammatory factors commonly found in atopic dermatitis and psoriasis, in particular IL-13 and IL-17. TWEAK is not a single etiological factor for atopic dermatitis or psoriasis, but it causes the production of chemokines that promote chemotaxis of pathogenic inflammatory cells into the skin. With further studies of this pathogenetic factor, it will be possible to synthesize a new targeted drug for the treatment of atopic dermatitis and psoriasis. 

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