vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v18i5.2064vsp-2238Research ArticleОБМЕН ОПЫТОМEXCHANGE OF EXPERIENCEСовременные представления о роли эпидермального барьера в развитии атопического фенотипа у детейModern View on the Role of Epidermal Barrier in Atopic Phenotype Development in Childrenhttps://orcid.org/0000-0003-2252-8570МурашкинН. Н.MurashkinNikolay N.

Мурашкин Николай Николаевич - доктор медицинских наук, профессор, заведующий отделением дерматологии с группой лазерной хирургии НМИЦ здоровья детей

119991, Москва, Ломоносовский пр-т, д. 2, стр. 1, тел.: +7 (499) 134-08-89

Moscow

m_nn2001@mail.ruhttps://orcid.org/0000-0001-6884-5171СавеловаА. А.SavelovaAlena A.

Москва

Moscow

https://orcid.org/0000-0002-0081-0981ИвановР. А.IvanovRoman A.

Москва

Moscow

https://orcid.org/0000-0001-9777-0156ФедоровД. В.FedorovDmitri V.

Москва

Moscow

https://orcid.org/0000-0002-0858-8780ОпрятинЛ. А.OpryatinLeonid A.

Москва

Moscow

https://orcid.org/0000-0002-4022-5592АхмадВ.AhmadWasel

Нальчик

Nal'chik

Национальный медицинский исследовательский центр здоровья детей; Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет); Центральная государственная медицинская академия Управления делами Президента Российской ФедерацииРоссияNational Medical Research Center of Children's Health; Sechenov First Moscow State Medical University (Sechenov University); Central State Medical Academy of Department of Presidential AffairsRussian FederationЦентральная государственная медицинская академия Управления делами Президента Российской ФедерацииРоссияCentral State Medical Academy of Department of Presidential AffairsRussian FederationНациональный медицинский исследовательский центр здоровья детейРоссияNational Medical Research Center of Children's HealthRussian FederationКабардино-Балкарский государственный университет им. Х.М. БербековаРоссияBerbekov Kabardino-Balkarian State UniversityRussian Federation201905012020185386392Copyright © Мурашкин Н.Н., Савелова А.А., Иванов Р.А., Федоров Д.В., Опрятин Л.А., Ахмад В., 20202020Мурашкин Н.Н., Савелова А.А., Иванов Р.А., Федоров Д.В., Опрятин Л.А., Ахмад В.Murashkin N.N., Savelova A.A., Ivanov R.A., Fedorov D.V., Opryatin L.A., Ahmad W.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/2238

Эпидермальный барьер является одной из важнейших структур кожи, которая отвечает за защитную функцию, обеспечивая постоянство внутренней среды организма за счет избирательного транспорта ионов и молекул и регуляции уровня трансэпидермальной потери воды. Биохимическую основу эпидермального барьера составляют сложные, интегрированные и сбалансированные молекулярные процессы, приводящие к гибели кератиноцитов путем их терминальной дифференцировки с заменой плазматической мембраны жестким нерастворимым макромолекулярным роговым слоем. Филаггрин и белки плотных соединений (tight junctions, TJs) являются важными структурными компонентами эпидермального барьера. Филаггрин после гидролиза способствует поддержанию pH, сохранению воды и защите кожи от микробных агентов. В свою очередь, белки TJ с активной экспрессией регулируют проницаемость эпидермиса, обеспечивая создание барьера к антигенам внешней среды.

Epidermal barrier is one is one of the most important structures of the skin, it performs protective function, ensure internal environment constancy by selective ions and molecules transport and by transepidermal water loss regulation. The biochemical basis of the epidermal barrier consists of complex, integrated and balanced molecular processes leading to keratinocytes death due to terminal differentiation and plasma membrane replacement with horny insoluble macromolecular stratum corneum. Filaggrin and tight junctions (TJs) proteins are important structural components of the epidermal barrier. Filaggrin, after hydrolysis, maintains pH level, preserves water, protects the skin from microbial agents. Whereas TJs proteins with active expression regulate epidermis permeability and create the barrier for exterior antigens.

детиэпидермальный барьерTJsтрансэпидермальная потеря водыкератиноцитыфилаггринроговой слойлипидные пластинытрансмембранные белкиpH кожитранскутанная IgE-сенсибилизацияchildrenepidermal barrierTJstransepidermal water losskeratinocytesfilaggrinstratum corneumlipid platestransmembrane proteinsskin pHtranscutaneous IgE-sensibilizationСтатья опубликована при поддержке ООО «Пьер Фабр»The article has been supported by Pierre Fabre LLCReferencesElias PM, Steinhoff M. «Outside-to-inside» (and now back to «outside») pathogenic mechanisms in atopic dermatitis. J Inv Derm. 2008;128(5):1067-1070. doi: 10.1038/jid.2008.88.Elias PM, Steinhoff M. «Outside-to-inside» (and now back to «outside») pathogenic mechanisms in atopic dermatitis. J Inv Derm. 2008;128(5):1067-1070. doi: 10.1038/jid.2008.88.Akdis CA, Akdis M, Bieber T, et al. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology / American Academy of Allergy, Asthma and Immunology / PRACTALL consensus report. Allergy. 2006;61(8):969-987. doi: 10.1111/j.1398-9995.2006.01153.x.Akdis CA, Akdis M, Bieber T, et al. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology / American Academy of Allergy, Asthma and Immunology / PRACTALL consensus report. Allergy. 2006;61(8):969-987. doi: 10.1111/j.1398-9995.2006.01153.x.Morar N, Willis-Owen SA, Moffatt MF, Cookson WO. The genetics of atopic dermatitis. J Allergy Clin Immunol. 2006;118(1):24-34. doi: 10.1016/j.jaci.2006.03.037.Morar N, Willis-Owen SA, Moffatt MF, Cookson WO. The genetics of atopic dermatitis. J Allergy Clin Immunol. 2006;118(1):24-34. doi: 10.1016/j.jaci.2006.03.037.Matsui T, Amagai M. Dissecting the formation, structure and barrier function of the stratum corneum. Int Immunol. 2015;27(6): 269-280. doi: 10.1093/intimm/dxv013.Matsui T, Amagai M. Dissecting the formation, structure and barrier function of the stratum corneum. Int Immunol. 2015;27(6): 269-280. doi: 10.1093/intimm/dxv013.Egawa G, Kabashima K. Barrier dysfunction in the skin allergy. Allergol Int. 2018;67(1):3-11. doi: 10.1016/j.alit.2017.10.002.Egawa G, Kabashima K. Barrier dysfunction in the skin allergy. Allergol Int. 2018;67(1):3-11. doi: 10.1016/j.alit.2017.10.002.Lund CH, Kuller J, Lane AT, et al. Neonatal skin care: evaluation of the AWHONN/NANN research-based practice project on knowledge and skin care practices. Association of Women's Health, Obstetric and Neonatal Nurses/National Association of Neonatal Nurses. J Obstet Gynecol Neonatal Nurs. 2001;30(1):30-40. doi: 10.1177/088421701129003842.Lund CH, Kuller J, Lane AT, et al. Neonatal skin care: evaluation of the AWHONN/NANN research-based practice project on knowledge and skin care practices. Association of Women's Health, Obstetric and Neonatal Nurses/National Association of Neonatal Nurses. J Obstet Gynecol Neonatal Nurs. 2001;30(1):30-40. doi: 10.1177/088421701129003842.Lund CH, Osborne JW, Kuller J, et al. Neonatal skin care: clinical outcomes of the AWHONN/NANN evidence-based clinical practice guideline. Association of Women's Health, Obstetric and Neonatal Nurses and the National Association of Neonatal Nurses. J Obstet Gynecol Neonatal Nurs. 2001;30(1):41-51. doi: 10.1177/088421701129003851.Lund CH, Osborne JW, Kuller J, et al. Neonatal skin care: clinical outcomes of the AWHONN/NANN evidence-based clinical practice guideline. Association of Women's Health, Obstetric and Neonatal Nurses and the National Association of Neonatal Nurses. J Obstet Gynecol Neonatal Nurs. 2001;30(1):41-51. doi: 10.1177/088421701129003851.Zhao LP Di Z, Zhang L, et al. Association of SPINK5 gene polymorphisms with atopic dermatitis in Northeast China. J Eur Acad Dermatol Venereol. 2012;26(5):572-577. doi: 10.1111/j.1468-3083.2011.04120.x.Zhao LP Di Z, Zhang L, et al. Association of SPINK5 gene polymorphisms with atopic dermatitis in Northeast China. J Eur Acad Dermatol Venereol. 2012;26(5):572-577. doi: 10.1111/j.1468-3083.2011.04120.x.O'Regan GM, Sandilands A, McLean WH, Irvine AD. Filaggrin in atopic dermatitis. J Allergy Clin Immunol. 2008;122(4):689-693. doi: 10.1016/j.jaci.2008.08.002.O'Regan GM, Sandilands A, McLean WH, Irvine AD. Filaggrin in atopic dermatitis. J Allergy Clin Immunol. 2008;122(4):689-693. doi: 10.1016/j.jaci.2008.08.002.Rawlings AV, Harding CR. Moisturization and skin barrier function. Dermatol Ther. 2004;17 Suppl 1:43-48. doi: 10.1111/j.1396-0296.2004.04s1005.x.Rawlings AV, Harding CR. Moisturization and skin barrier function. Dermatol Ther. 2004;17 Suppl 1:43-48. doi: 10.1111/j.1396-0296.2004.04s1005.x.Thyssen JP, Kezic S. Causes of epidermal filaggrin reduction and their role in the pathogenesis of atopic dermatitis. J Allergy Clin Immunol. 2014;134(4):792-799. doi: 10.1016/ j.jaci.2014.06.014.Thyssen JP, Kezic S. Causes of epidermal filaggrin reduction and their role in the pathogenesis of atopic dermatitis. J Allergy Clin Immunol. 2014;134(4):792-799. doi: 10.1016/ j.jaci.2014.06.014.Miajlovic H, Fallon PG, Irvine AD, Foster TJ. Effect of filag-grin breakdown products on growth of and protein expression by Staphylococcus aureus. J Allergy Clin Immunol. 2010;126(6): 1184-1190.e3. doi: 10.1016/j.jaci.2010.09.015.Miajlovic H, Fallon PG, Irvine AD, Foster TJ. Effect of filag-grin breakdown products on growth of and protein expression by Staphylococcus aureus. J Allergy Clin Immunol. 2010;126(6): 1184-1190.e3. doi: 10.1016/j.jaci.2010.09.015.Hammarlund K, Sedin G, Stromberg B. Transepidermal water loss in newborn infants. VIII. Relation to gestational age and postnatal age in appropriate and small for gestational age infants. Acta Paediatr Scand. 1983;72(5):721-728. doi: 10.1111/j.1651-2227.1983.tb09801.x.Hammarlund K, Sedin G, Stromberg B. Transepidermal water loss in newborn infants. VIII. Relation to gestational age and postnatal age in appropriate and small for gestational age infants. Acta Paediatr Scand. 1983;72(5):721-728. doi: 10.1111/j.1651-2227.1983.tb09801.x.Irvine AD, Hoeger PH, Yan AC. Harper’s Textbook of Pediatric Dermatology. Wiley-Blackwell; 2011.Irvine AD, Hoeger PH, Yan AC. Harper’s Textbook of Pediatric Dermatology. Wiley-Blackwell; 2011.McCall EM, Alderdice F, Halliday HL, et al. Interventions to prevent hypothermia at birth in preterm and/or low birthweight infants. Cochrane Database Syst Rev. 2010;(3):CD004210. doi: 10.1002/14651858.CD004210.pub4.McCall EM, Alderdice F, Halliday HL, et al. Interventions to prevent hypothermia at birth in preterm and/or low birthweight infants. Cochrane Database Syst Rev. 2010;(3):CD004210. doi: 10.1002/14651858.CD004210.pub4.Eichenfield LF, Frieden IJ, Mathes E, Zaenglein A. Neonatal and Infant Dermatology. Elsevier Inc; 2015. 752 р.Eichenfield LF, Frieden IJ, Mathes E, Zaenglein A. Neonatal and Infant Dermatology. Elsevier Inc; 2015. 752 р.Zaniboni MC, Samorano LP, Orfali RL, Aoki V. Skin barrier in atopic dermatitis: beyond filaggrin. An Bras Dermatol. 2016;91(4): 472-478. doi: 10.1590/abd1806-4841.20164412.Zaniboni MC, Samorano LP, Orfali RL, Aoki V. Skin barrier in atopic dermatitis: beyond filaggrin. An Bras Dermatol. 2016;91(4): 472-478. doi: 10.1590/abd1806-4841.20164412.Brown SJ, Asai Y, Cordell HJ, et al. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol. 2011;127(3):661-667. doi: 10.1016/j.jaci.2011.01.031.Brown SJ, Asai Y, Cordell HJ, et al. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol. 2011;127(3):661-667. doi: 10.1016/j.jaci.2011.01.031.Deraison C, Bonnart C, Lopez F, et al. LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction. Mol Biol Cell. 2007;18(9): 3607-3619. doi: 10.1091/mbc.e07-02-0124.Deraison C, Bonnart C, Lopez F, et al. LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction. Mol Biol Cell. 2007;18(9): 3607-3619. doi: 10.1091/mbc.e07-02-0124.Looman KIM, van Meel ER, Grosserichter-Wagener C, et al. Associations of Th2, Th17, Treg cells, and IgA + memory B cells with atopic disease in children: the generation R study. Allergy. 2019 Aug 6. doi: 10.1111/all.14010.Looman KIM, van Meel ER, Grosserichter-Wagener C, et al. Associations of Th2, Th17, Treg cells, and IgA + memory B cells with atopic disease in children: the generation R study. Allergy. 2019 Aug 6. doi: 10.1111/all.14010.Filho GH, Cunhain PR. Fogo Selvagem (Endemic Pemphigus Foliaceus). In: Tyring SK. Tropical Dermatology (Second Edition). Elsevier; 2017.Filho GH, Cunhain PR. Fogo Selvagem (Endemic Pemphigus Foliaceus). In: Tyring SK. Tropical Dermatology (Second Edition). Elsevier; 2017.Samuelov L, Sarig O, Harmon RM, et al. Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nat Genet. 2013;45(10):1244-1248. doi: 10.1038/ng.2739.Samuelov L, Sarig O, Harmon RM, et al. Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nat Genet. 2013;45(10):1244-1248. doi: 10.1038/ng.2739.Oji V, Eckl KM, Aufenvenne K, et al. Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: unraveling the peeling skin disease. Am J Hum Genet. 2010;87(2):274-281. doi: 10.1016/j.ajhg.2010.07.005.Oji V, Eckl KM, Aufenvenne K, et al. Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: unraveling the peeling skin disease. Am J Hum Genet. 2010;87(2):274-281. doi: 10.1016/j.ajhg.2010.07.005.Brattsand M, Stefansson K, Lundh C, et al. A proteolytic cascade of kallikreins in the stratum corneum. J Invest Dermatol. 2005;124(1):198-203. doi: 10.1111/j.0022-202X.2004.23547.x.Brattsand M, Stefansson K, Lundh C, et al. A proteolytic cascade of kallikreins in the stratum corneum. J Invest Dermatol. 2005;124(1):198-203. doi: 10.1111/j.0022-202X.2004.23547.x.Krieg P Furstenberger G. The role of lipoxygenases in epidermis. Biochim Biophys Acta. 2014;1841(3):390-400. doi: 10.1016/j.bbalip.2013.08.005.Krieg P Furstenberger G. The role of lipoxygenases in epidermis. Biochim Biophys Acta. 2014;1841(3):390-400. doi: 10.1016/j.bbalip.2013.08.005.Egawa G, Kabashima K. Multifactorial skin barrier deficiency and atopic dermatitis: Essential topics to prevent the atopic march. J Allergy Clin Immunol. 2016;138(2):350-358.e1. doi: 10.1016/j.jaci.2016.06.002.Egawa G, Kabashima K. Multifactorial skin barrier deficiency and atopic dermatitis: Essential topics to prevent the atopic march. J Allergy Clin Immunol. 2016;138(2):350-358.e1. doi: 10.1016/j.jaci.2016.06.002.Sasaki T, Shiohama A, Kubo A, et al. A homozygous nonsense mutation in the gene for Tmem79, a component for the lamellar granule secretory system, produces spontaneous eczema in an experimental model of atopic dermatitis. J Allergy Clin Immunol. 2013;132(5):1111-1120.e4. doi: 10.1016/j.jaci.2013.08.027.Sasaki T, Shiohama A, Kubo A, et al. A homozygous nonsense mutation in the gene for Tmem79, a component for the lamellar granule secretory system, produces spontaneous eczema in an experimental model of atopic dermatitis. J Allergy Clin Immunol. 2013;132(5):1111-1120.e4. doi: 10.1016/j.jaci.2013.08.027.Saunders SP, Goh CS, Brown SJ, et al. Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in human subjects. J Allergy Clin Immunol. 2013;132(5):1121-1129. doi: 10.1016/j.jaci.2013.08.046.Saunders SP, Goh CS, Brown SJ, et al. Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in human subjects. J Allergy Clin Immunol. 2013;132(5):1121-1129. doi: 10.1016/j.jaci.2013.08.046.Skabytska Y, Kaesler S, Volz T, Biedermann T. The role of innate immune signaling in the pathogenesis of atopic dermatitis and consequences for treatments. Semin Immunopathol. 2016;38(1): 29-43. doi: 10.1007/s00281-015-0544-y.Skabytska Y, Kaesler S, Volz T, Biedermann T. The role of innate immune signaling in the pathogenesis of atopic dermatitis and consequences for treatments. Semin Immunopathol. 2016;38(1): 29-43. doi: 10.1007/s00281-015-0544-y.Jiang D, Liang J, Fan J, et al. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat Med. 2005;11(11): 1173-1179. doi: 10.1038/nm1315.Jiang D, Liang J, Fan J, et al. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat Med. 2005;11(11): 1173-1179. doi: 10.1038/nm1315.Schroder K, Tschopp J. The inflammasomes. Cell. 2010; 140(6):821-832. doi: 10.1016/j.cell.2010.01.040.Schroder K, Tschopp J. The inflammasomes. Cell. 2010; 140(6):821-832. doi: 10.1016/j.cell.2010.01.040.De Benedetto A, Agnihothri R, McGirt LY, et al. Atopic dermatitis: a disease caused by innate immune defects? J Invest Dermatol. 2009;129(1):14-30. doi: 10.1038/jid.2008.259.De Benedetto A, Agnihothri R, McGirt LY, et al. Atopic dermatitis: a disease caused by innate immune defects? J Invest Dermatol. 2009;129(1):14-30. doi: 10.1038/jid.2008.259.Weidinger S, Klopp N, Rummler L, et al. Association of NOD1 polymorphisms with atopic eczema and related phenotypes. J Allergy Clin Immunol. 2005;116(1):177-184. doi: 10.1016/j.jaci.2005.02.034.Weidinger S, Klopp N, Rummler L, et al. Association of NOD1 polymorphisms with atopic eczema and related phenotypes. J Allergy Clin Immunol. 2005;116(1):177-184. doi: 10.1016/j.jaci.2005.02.034.Weidinger S, Klopp N, Rummler L, et al. Association of CARD15 polymorphisms with atopy-related traits in a population based cohort of Caucasian adults. Clin Exp Allergy. 2005;35(7):866-872. doi: 10.1111/j.1365-2222.2005.02269.x.Weidinger S, Klopp N, Rummler L, et al. Association of CARD15 polymorphisms with atopy-related traits in a population based cohort of Caucasian adults. Clin Exp Allergy. 2005;35(7):866-872. doi: 10.1111/j.1365-2222.2005.02269.x.Gschwandtner M, Mildner M, Mlitz V, et al. Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model. Allergy. 2013;68(1):37-47. doi: 10.1111/all.12051.Gschwandtner M, Mildner M, Mlitz V, et al. Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model. Allergy. 2013;68(1):37-47. doi: 10.1111/all.12051.Gutowska-Owsiak D, Schaupp AL, Salimi M, et al. IL-17 down-regulates filaggrin and affects keratinocyte expression of genes associated with cellular adhesion. Exp Dermatol. 2012;21(2): 104-110. doi: 10.1111/j.1600-0625.2011.01412.x.Gutowska-Owsiak D, Schaupp AL, Salimi M, et al. IL-17 down-regulates filaggrin and affects keratinocyte expression of genes associated with cellular adhesion. Exp Dermatol. 2012;21(2): 104-110. doi: 10.1111/j.1600-0625.2011.01412.x.Gutowska-Owsiak D, Schaupp AL, Salimi M, et al. Interleukin-22 downregulates filaggrin expression and affects expression of profil-aggrin processing enzymes. Br J Dermatol. 2011;165(3):492-498. doi: 10.1111/j.1365-2133.2011.10400.x.Gutowska-Owsiak D, Schaupp AL, Salimi M, et al. Interleukin-22 downregulates filaggrin expression and affects expression of profil-aggrin processing enzymes. Br J Dermatol. 2011;165(3):492-498. doi: 10.1111/j.1365-2133.2011.10400.x.Orfali RL, Sato MN, Takaoka R, et al. Atopic dermatitis in adults: evaluation of peripheral blood mononuclear cells proliferation response to Staphylococcus aureus enterotoxins A and B and analysis of interleukin-18 secretion. Exp Dermatol. 2009;18(7): 628-633. doi: 10.1111/j.1600-0625.2009.00842.x.Orfali RL, Sato MN, Takaoka R, et al. Atopic dermatitis in adults: evaluation of peripheral blood mononuclear cells proliferation response to Staphylococcus aureus enterotoxins A and B and analysis of interleukin-18 secretion. Exp Dermatol. 2009;18(7): 628-633. doi: 10.1111/j.1600-0625.2009.00842.x.Howell MD, Kim BE, Gao P, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2009;124(3 Suppl 2):R7-R12. doi: 10.1016/j.jaci.2009.07.012.Howell MD, Kim BE, Gao P, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2009;124(3 Suppl 2):R7-R12. doi: 10.1016/j.jaci.2009.07.012.Hadj-Rabia S, Baala L, Vabres P et al. Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. Gastroenterology. 2004;127(5):1386-1390. doi: 10.1053/j.gastro.2004.07.022.Hadj-Rabia S, Baala L, Vabres P et al. Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. Gastroenterology. 2004;127(5):1386-1390. doi: 10.1053/j.gastro.2004.07.022.Turksen K, Troy TC. Barriers built on claudins. J Cell Sci. 2004;117(Pt 12):2435-2447. doi: 10.1242/jcs.01235.Turksen K, Troy TC. Barriers built on claudins. J Cell Sci. 2004;117(Pt 12):2435-2447. doi: 10.1242/jcs.01235.Yuki T, Yoshida H, Akazawa Y, et al. Activation of TLR2 enhances tight junction barrier in epidermal keratinocytes. J Immunol. 2011;187(6):3230-3237. doi: 10.4049/jimmunol.1100058.Yuki T, Yoshida H, Akazawa Y, et al. Activation of TLR2 enhances tight junction barrier in epidermal keratinocytes. J Immunol. 2011;187(6):3230-3237. doi: 10.4049/jimmunol.1100058.De Benedetto A, Rafaels NM, McGirt LY, et al. Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol. 2011;127(3):773-786.e1-7. doi: 10.1016/j.jaci.2010.10.018.De Benedetto A, Rafaels NM, McGirt LY, et al. Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol. 2011;127(3):773-786.e1-7. doi: 10.1016/j.jaci.2010.10.018.Yokouchi M, Kubo A, Kawasaki H, et al. Epidermal tight junction barrier function is altered by skin inflammation, but not by filag-grindeficient stratum corneum. J Dermatol Sci. 2015;77(1):28-36. doi: 10.1016/j.jdermsci.2014.11.007.Yokouchi M, Kubo A, Kawasaki H, et al. Epidermal tight junction barrier function is altered by skin inflammation, but not by filag-grindeficient stratum corneum. J Dermatol Sci. 2015;77(1):28-36. doi: 10.1016/j.jdermsci.2014.11.007.Aries MF, Vaissiere C, Delga H, et al. Antiinflammatory and immunomodulatory effects of I-modulia, an Aquaphilus dolomiae extract, on atopic dermatitis in vitro. J Am Acad Dermatol. 2014; 70(5 Suppl 1):АВ61. doi: 10.1016/j.jaad.2014.01.253.Aries MF, Vaissiere C, Delga H, et al. Antiinflammatory and immunomodulatory effects of I-modulia, an Aquaphilus dolomiae extract, on atopic dermatitis in vitro. J Am Acad Dermatol. 2014; 70(5 Suppl 1):АВ61. doi: 10.1016/j.jaad.2014.01.253.Nguyen T, Castex-Rizzi N, Redoules D. Activites immunomodula-trice, anti-inflammatoire, antiprurigineuse et tolerogenique induites par I-modulia, un extrait issu de culture dAquaphilus dolomi-ae, dans les modeles pharmacologiques de dermatite atopique. Ann Derm Vеnеrеol. 2017;144:S42-S49. doi: 10.1016/s01519638(17)31042-6.Nguyen T, Castex-Rizzi N, Redoules D. Activites immunomodula-trice, anti-inflammatoire, antiprurigineuse et tolerogenique induites par I-modulia, un extrait issu de culture dAquaphilus dolomi-ae, dans les modeles pharmacologiques de dermatite atopique. Ann Derm Vеnеrеol. 2017;144:S42-S49. doi: 10.1016/s01519638(17)31042-6.

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