Russian Journal of AllergyRussian Journal of AllergyРоссийский Аллергологический Журнал1810-88302686-682XPublishing House ABV Press54910.36691/RJA549ArticlesСтатьиResearch ArticleSkin barrier: structure and immune changes in common skin diseasesКожный барьер: структурные и иммунные изменения при распространенных болезнях кожиIonescuMarius-Anton AntonИонескуМариус Антон

MD, PhD

dr.toni.ionescu@gmail.comDermatology Outpatient Clinic «Saint-Louis» University HospitalДерматологическая поликлиника Университетского госпиталя Сан-Луи15042014112NO2 (2014)№2 (2014)838910032020Copyright ©; 2014, Pharmarus Print MediaCopyright ©; 2014, Фармарус Принт Медиа2014Pharmarus Print MediaФармарус Принт Медиаhttps://rusalljournal.ru/raj/article/view/549

Skin barrier must be seen as a complex structure with complex functions involving hydrolipidic film, stratum corneum, the intercellular cement and also immunologic barrier as innate adaptive immune system (as Toll Like Receptors - TLR), complement, dendritic cells and antigen-related responses. Skin barrier changes are seen in different skin diseases as atopic dermatitis, rosacea , contact dermatitis and others. In the first part of this article we describe skin physical barrier and its key elements roles (ceramides, filaggrin, tight junctions and claudins), the clinical consequences of barrier damages in different common skin diseases (atopic dermatitis, xeroses of different origins). Immune skin barrier is complex and in this first part of the article we focus only on innate immune system skin represented by Toll Like Receptors and their role in the synthesis of antimicrobial peptides (AMP). In the second part we present ex vivo and in vivo studies on skin physical barrier repair and improvement of AMP expression in human skin by modulating TLR2. The management of human skin barrier damages and their repair by active topicals must by a holistic approach, taking in account the complexity of physical and of immune barriers of the skin.

Кожный барьер - это сложная структура с многогранными функциями, включающая в себя гидролипидную пленку, роговой слой, межклеточный цемент, а также линию иммунологической защиты - часть врожденной иммунной системы (Toll-подобные рецепторы - TLR), комплемент, дендритные клетки и антиген-зависимые реакции. Изменения в кожном барьере наблюдаются при различных заболеваниях кожи, таких как атопический дерматит (АтД), розацеа, контактный дерматит и др. В первой части статьи описывается структурный кожный барьер и функции его ключевых элементов (церамиды, филаггрин, плотные контакты и клаудины), клинические последствия нарушений барьера при различных заболеваниях (АтД, ксерозы различной этиологии). рассмотрена система врожденного иммунитета кожи, представленного TLR, и участие TLR в синтезе антимикробных пептидов (АМП). Во второй части представлены проведенные ex vivo и in vivo исследования восстановления поврежденного структурного кожного барьера и повышение экспрессии АМП в коже человека при модулирующем действии на TLR2. Учитывая сложность структурного и иммунного барьеров кожи, местное терапевтическое лечение при их нарушении требует комплексного подхода.

skin barrierskin diseasesantimicrobial peptidesкожный барьерзаболевания кожиантимикробные пептидыBouwstra J.A., Honeywell-Nguyen P.L., Gooris G.S. et al. Structure of the skin barrier and its modulation by vesicular formulations. Prog. Lipid. Res. 2003, v. 42 (1), p. 1-36.Rawlings A.V. Trends in stratum corneum research and the management of dry skin conditions. Int. J. Cosmet. Sci. 2003, v. 25, p. 63-95.Boralevi F. Dermatite atopique en 2012: «in and out». Réal thér dermato-vénérol. 2012, v. 220, p. 41-43.Furuse M., Fujita K., Hiiragi T. et al. Claudin-1 and-2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. Cell Biol. 1998, v. 141 (7), p. 1539-1550.Richard GALLO. Antimicrobial peptides (AMP) AAD Meeting San Diego 2012.Nakatsuji T., Chiang H.I. 2,4, Jiang S.B., Nagarajan H. et al. The microbiome extends to subepidermal compartments of normal skin. Nat. Commun. 2013, v. 4, p. 1431.Jann N.J., Schmaler M., Kristian S.A. et al. Neutrophil antimicrobial defense against Staphylococcus aureus is mediated by phagolysosomal but not extracellular trap-associated cathelicidin. J. Leukoc Biol. 2009, v. 86 (5), p. 1159-1169.Braff M.H., Zaiou M., Fierer J. et al. Keratinocyte production of cathelicidin provides direct activity against bacterial skin pathogens. Infect. Immun. 2005, v. 73 (10), p. 6771-6781.Nakatsuji T., Gallo R.L. Antimicrobial peptides: old molecules with new ideas. J. Invest. Dermatol. 2012, v. 132 (3 Pt. 2), p. 887-895.Schröder J.M. Antimicrobial peptides in healthy skin and atopic dermatitis. Allergol. Int. 2011, v. 60 (1), p. 17-24.Schittek B. The antimicrobial skin barrier in patients with atopic dermatitis. Curr. Probl. Dermatol. 2011, v. 41, p. 54-67.Yamasaki K., Di Nardo A., Bardan A. et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea.Nat. Med. 2007, v. 13 (8), p. 975-980.Yamasaki K., Kanada K., Macleod D.T et al. TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes. J. Invest. Dermatol. 2011, v. 131 (3), p. 688-697.Lai Y., Di Nardo A., Nakatsuji T et al. Commensal bacteria regulate Toll-like receptor 3-dependent inflammation after skin injury. Nat. Med. 2009, v. 15 (12), p. 1377-1382.Joly F., Gardille C., Barbieux E., Lefeuvre L. Beneficial effect of a thermal spring water on the skin barrier recovery after injury: Evidence for claudin-6 expression in human skin. J. Cosm. Dermatol. Sci. Applications. 2012, v. 2, p. 273-276.Ionescu M.A., Joly F., Gardille F., Barbieux E., Lefeuvre L. Modulation of epidermal barrier markers filaggrin and claudins. EADV Istanbul. 2013. Poster P177.Kang S.S.W., Kauls L., Gaspary A.A. Toll-like receptors: Applications to dermatologic disease. J. Am. Acad. Dermatol. 2006, v. 54, p. 951-983.Ionescu M.A., Baroni A., Brambilla L. et al. Double blind clinical trial in a series of 115 patients with seborrheic dermatitis: prevention of relapses using a topical modulator of Toll like receptor 2. G Ital. Dermatol. Venereol. 2011, v. 146, p. 185-189.Aliprantis A.O., Yang R.B., Mark M.R. et al. Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Science. 1999, v. 285, p. 736-739.Baroni A., Orlando M., Donnarumma G. et al. Toll-like receptor 2 (TLR2) mediates intracellular signalling in human keratinocytes in response to Malassezia furfur. Arch. Dermatol. Res. 2006, v. 297, p. 280-288.Pivarcsi A., Bodai L., Rйthi B. et al. Expression and function of Toll-like receptors 2 and 4 in human keratinocytes.Int. Immunol. 2003, v. 15, p. 721-730.Donnarumma G., Paoletti I., Buommino E. et al. Malassezia furfur induces the expression of beta-defensin-2 in human keratinocytes in a protein kinase C-dependent manner. Arch. Dermatol. Res. 2004, v. 295, p. 474-481.