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Tight junctions in skin inflammation

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Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Inflammation of the skin is found after various external stimuli, e.g., UV radiation, allergen uptake, microbial challenge, or contact with irritants, as well as due to intrinsic, not always well-defined, stimuli, e.g., in autoimmune responses. Often, it is also triggered by a combination of both. The specific processes, which mean the kind of cytokines and immune cells involved and the extent of the reaction, depend not only on the trigger but also on the predisposition of the individual. Tight junctions (TJs) in the skin have been shown to form a barrier in the granular cell layer of the epidermis. Furthermore, TJ proteins were found in several additional epidermal layers. Besides barrier function, TJ proteins have been shown to be involved in proliferation, differentiation, cell-cell adhesion, and apoptosis in keratinocytes. In inflamed skin, TJ proteins are often affected. We summarize here the impact of skin inflammation on TJs, e.g., in various forms of dermatitis including atopic dermatitis, in skin infection, and in UV-irradiated skin, and discuss the role of TJs in these inflammatory processes.

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References

  1. Adams MP, Mallet DG, Pettet GJ (2015) Towards a quantitative theory of epidermal calcium profile formation in unwounded skin. PLoS One 10:e0116751

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Ahdieh M, Vandenbos T, Youakim A (2001) Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-γ. Am J Physiol Cell Physiol 281:C2029–C2038

    CAS  PubMed  Google Scholar 

  3. Akiyama T, Niyonsaba F, Kiatsurayanon C, Nguyen TT, Ushio H, Fujimura T, Ueno T, Okumura K, Ogawa H, Ikeda S (2014) The human cathelicidin LL-37 host defense peptide upregulates tight junction-related proteins and increases human epidermal keratinocyte barrier function. J Innate Immun 6(6):739–753

  4. Alessi E, Caputo R (2013) Histology of the skin and skin appendages. In: Giannetti A (ed) Textbook of dermatology & sexually transmitted diseases. Picci Nuova Libraria S.P.A, Padova, pp 25–59

    Google Scholar 

  5. Anderson JM (2001) Molecular structure of tight junctions and their role in epithelial transport. News Physiol Sci 16:126–130

    CAS  PubMed  Google Scholar 

  6. Aono S, Hirai Y (2008) Phosphorylation of claudin-4 is required for tight junction formation in a human keratinocyte cell line. Exp Cell Res 314:3326–3339

    Article  CAS  PubMed  Google Scholar 

  7. Asad S, Winge MCG, Wahlgren CF, Bilcha KD, Nordenskjöld M, Taylan F, Bradley M (2016) The tight junction gene Claudin-1 is associated with atopic dermatitis among Ethiopians. J Eur Acad Dermatol Venerol 30:1939–1941

    CAS  Google Scholar 

  8. Barnes KC (2010) An update on the genetics of atopic dermatitis: scratching the surface in 2009. J Aller Clin Immunol 125:16–29.e11

    Article  CAS  Google Scholar 

  9. Bäsler K, Bergmann S, Heisig M, Naegel A, Zorn-Kruppa M, Brandner JM (2016) The role of tight junctions in skin barrier function and dermal absorption. J Control Release. doi:10.1016/j.jconrel.2016.08.007

    PubMed  Google Scholar 

  10. Batista DI, Perez L, Orfali RL, Zaniboni MC, Samorano LP, Pereira NV, Sotto MN, Ishizaki AS, Oliveira LM, Sato MN, Aoki V (2015) Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1/Th2/Th17 cytokines in adults with atopic dermatitis. J Eur Acad Dermatol Venereol 29:1091–1095

    Article  CAS  PubMed  Google Scholar 

  11. Behrends U, Eißner G, Bornkamm GW, Peter RU, Hintermeier-Knabe R, Holler E, Caughman SW, Degitz K (1994) Ionizing radiation induces human intercellular adhesion molecule-1 in vitro. J Invest Dermatol 103:726–730

    Article  CAS  PubMed  Google Scholar 

  12. Borkowski AW, Kuo IH, Bernard JJ, Yoshida T, Williams MR, Hung NJ, Yu BD, Beck LA, Gallo RL (2015) Toll-like receptor 3 activation is required for normal skin barrier repair following UV damage. J Invest Dermatol 135:569–578

    Article  CAS  PubMed  Google Scholar 

  13. Brandner JM (2009) Tight junctions and tight junction proteins in mammalian epidermis. Eur J Pharm Biopharm 72:289–294

    Article  CAS  PubMed  Google Scholar 

  14. Brandner JM, Kief S, Grund C, Rendl M, Houdek P, Kuhn C, Tschachler E, Franke WW, Moll I (2002) Organization and formation of the tight junction system in human epidermis and cultured keratinocytes. Eur J Cell Biol 81:253–263

    Article  CAS  PubMed  Google Scholar 

  15. Brandner JM, Schulzke JD (2015) Hereditary barrier-related diseases involving the tight junction: lessons from skin and intestine. Cell Tissue Res 360:723–748

    Article  PubMed  Google Scholar 

  16. Brown SJ (2016) Molecular mechanisms in atopic eczema: insight gained from genetic studies. J Pathol. doi:10.1002/path.4810

    PubMed Central  Google Scholar 

  17. Canil C, Rosenshine I, Ruschkowski S, Donnenberg MS, Kaper JB, Finlay BB (1993) Enteropathogenic Escherichia coli decreases the transepithelial electrical resistance of polarized epithelial monolayers. Infect Immun 61:2755–2762

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Chodaczek G, Papanna V, Zal MA, Zal T (2012) Body-barrier surveillance by epidermal [gamma][delta] TCRs. Nat Immunol 13:272–282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Clemmensen A, Andersen KE, Clemmensen O, Tan Q, Petersen TK, Kruse TA, Thomassen M (2010) Genome-wide expression analysis of human in vivo irritated epidermis: differential profiles induced by sodium lauryl sulfate and nonanoic acid. J Invest Dermatol 130:2201–2210

    Article  CAS  PubMed  Google Scholar 

  20. Clydesdale GJ, Dandie GW, Muller HK (2001) Ultraviolet light induced injury: immunological and inflammatory effects. Immunol Cell Biol 79:547–568

    Article  CAS  PubMed  Google Scholar 

  21. Cork MJ, Danby SG, Vasilopoulos Y, Hadgraft J, Lane ME, Moustafa M, Guy RH, MacGowan AL, Tazi-Ahnini R, Ward SJ (2009) Epidermal barrier dysfunction in atopic dermatitis. J Invest Dermatol 129:1892–1908

    Article  CAS  PubMed  Google Scholar 

  22. D’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T (2013) UV radiation and the skin. Int J Mol Sci 14:12222–12248

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Danso MO, van Drongelen V, Mulder A, van Esch J, Scott H, van Smeden J, El Ghalbzouri A, Bouwstra JA (2014) TNF-α and Th2 cytokines induce atopic dermatitis–like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents. J Invest Dermatol 134:1941–1950

    Article  CAS  PubMed  Google Scholar 

  24. De Benedetto A, Rafaels NM, McGirt LY, Ivanov AI, Georas SN, Cheadle C, Berger AE, Zhang K, Vidyasagar S, Yoshida T, Boguniewicz M, Hata T, Schneider LC, Hanifin JM, Gallo RL, Novak N, Weidinger S, Beaty TH, Leung DY, Barnes KC, Beck LA (2011) Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol 127:773–786 e771-777

    Article  CAS  PubMed  Google Scholar 

  25. De Benedetto A, Slifka MK, Rafaels NM, Kuo IH, Georas SN, Boguniewicz M, Hata T, Schneider LC, Hanifin JM, Gallo RL, Johnson DC, Barnes KC, Leung DY, Beck LA (2011) Reductions in claudin-1 may enhance susceptibility to herpes simplex virus 1 infections in atopic dermatitis. J Allergy Clin Immunol 128:242–246.e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Eberlein-Konig B, Schafer T, Huss-Marp J, Darsow U, Mohrenschlager M, Herbert O, Abeck D, Kramer U, Behrendt H, Ring J (2000) Skin surface pH, stratum corneum hydration, trans-epidermal water loss and skin roughness related to atopic eczema and skin dryness in a population of primary school children. Acta Derm Venereol 80:188–191

    Article  CAS  PubMed  Google Scholar 

  27. Elias PM (1988) Structure and function of the stratum corneum permeability barrier. Drug Dev Res 13:97–105

    Article  CAS  Google Scholar 

  28. Elias PM, Schmuth M (2009) Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Curr Allergy Asthma Rep 9:265–272

    Article  CAS  PubMed  Google Scholar 

  29. Enikanolaiye A, Lariviere N, Troy TC, Arabzadeh A, Atasoy E, Turksen K (2010) Involucrin-claudin-6 tail deletion mutant (CDelta206) transgenic mice: a model of delayed epidermal permeability barrier formation and repair. Dis Model Mech 3:167–180

    Article  CAS  PubMed  Google Scholar 

  30. Eyerich K, Novak N (2013) Immunology of atopic eczema: overcoming the Th1/Th2 paradigm. Allergy 68:974–982

    Article  CAS  PubMed  Google Scholar 

  31. Feldmeyer L, Huber M, Fellmann F, Beckmann JS, Frenk E, Hohl D (2006) Confirmation of the origin of NISCH syndrome. Hum Mutat 27:408–410

    Article  CAS  PubMed  Google Scholar 

  32. Fuchs J, Kern H (1998) Modulation of UV-light-induced skin inflammation by d-alpha-tocopherol and l-ascorbic acid: a clinical study using solar simulated radiation. Free Radic Biol Med 25:1006–1012

    Article  CAS  PubMed  Google Scholar 

  33. Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, Noda T, Kubo A, Tsukita S (2002) Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol 156:1099–1111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Garnacho-Saucedo G, Salido-Vallejo R, Moreno-Gimenez JC (2013) Atopic dermatitis: update and proposed management algorithm. Actas Dermosifiliogr 104:4–16

    Article  CAS  PubMed  Google Scholar 

  35. Girolomoni G, Pastore S, Cavani A (2013) Skin immune system. In: Giannetti A (ed) Textbook of dermatology & sexually transmitted diseases. Piccini Nuova Libraria S.P.A, Padova, pp 122–136

    Google Scholar 

  36. Gröger S, Michel J, Meyle J (2008) Establishment and characterization of immortalized human gingival keratinocyte cell lines. J Periodontal Res 43:604–614

    Article  PubMed  Google Scholar 

  37. Gruber R, Bornchen C, Rose K, Daubmann A, Volksdorf T, Wladykowski E, Vidal YSS, Peters EM, Danso M, Bouwstra JA, Hennies HC, Moll I, Schmuth M, Brandner JM (2015) Diverse regulation of claudin-1 and claudin-4 in atopic dermatitis. Am J Pathol 185:2777–2789

    Article  CAS  PubMed  Google Scholar 

  38. Gschwandtner M, Mildner M, Mlitz V, Gruber F, Eckhart L, Werfel T, Gutzmer R, Elias PM, Tschachler E (2013) Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model. Allergy 68:37–47

    Article  CAS  PubMed  Google Scholar 

  39. Gutowska-Owsiak D, Schaupp AL, Salimi M, Selvakumar TA, McPherson T, Taylor S, Ogg GS (2012) IL-17 downregulates filaggrin and affects keratinocyte expression of genes associated with cellular adhesion. Exp Dermatol 21:104–110

    Article  CAS  PubMed  Google Scholar 

  40. Guttman JA, Finlay BB (2009) Tight junctions as targets of infectious agents. BBA-Biomembranes 1788:832–841

    Article  CAS  PubMed  Google Scholar 

  41. Hadj-Rabia S, Baala L, Vabres P, Hamel-Teillac D, Jacquemin E, Fabre M, Lyonnet S, De Prost Y, Munnich A, Hadchouel M, Smahi A (2004) Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. Gastroenterology 127:1386–1390

    Article  CAS  PubMed  Google Scholar 

  42. Hashimoto K (1971) Intercellular spaces of the human epidermis as demonstrated with lanthanum. J Invest Dermatol 57:17–31

    Article  CAS  PubMed  Google Scholar 

  43. Hattori F, Kiatsurayanon C, Okumura K, Ogawa H, Ikeda S, Okamoto K, and Niyonsaba F. The antimicrobial protein S100A7/psoriasin enhances expression of keratinocyte differentiation markers and strengthens the skin tight junction barrier. Br J Dermatol 171:742–753 2014.

  44. Hedrich CM (2016) Shaping the spectrum—from autoinflammation to autoimmunity. Clin Immunol 165:21–28

    Article  CAS  PubMed  Google Scholar 

  45. Ho KK, Campbell KL, Lavergne SN (2015) Contact dermatitis: a comparative and translational review of the literature. Vet Dermatol 26:314–327 e366-317

    Article  PubMed  Google Scholar 

  46. Holgate ST (2007) Epithelium dysfunction in asthma. J Allergy Clin Immunol 120:1233–1244 quiz 1245-1236

    Article  CAS  PubMed  Google Scholar 

  47. Hönzke S, Wallmeyer L, Ostrowski A, Radbruch M, Mundhenk L, Schafer-Korting M, Hedtrich S (2016) Influence of Th2 cytokines on the cornified envelope, tight junction proteins, and ?-defensins in filaggrin-deficient skin equivalents. J Invest Dermatol 136:631–639

    Article  PubMed  CAS  Google Scholar 

  48. Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, DeBenedetto A, Schneider L, Beck LA, Barnes KC, Leung DYM (2007) Cytokine modulation of atopic dermatitis filaggrin skin expression. J Aller Clin Immunol 120:150–155

    Article  CAS  Google Scholar 

  49. Huang JT, Abrams M, Tlougan B, Rademaker A, Paller AS (2009) Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity. Pediatrics 123:e808–e814

    Article  PubMed  Google Scholar 

  50. Imokawa G, Abe A, Jin K, Higaki Y, Kawashima M, Hidano A (1991) Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin? J Invest Dermatol 96:523–526

    Article  CAS  PubMed  Google Scholar 

  51. Ishida-Yamamoto A, Kishibe M, Murakami M, Honma M, Takahashi H, Iizuka H (2012) Lamellar granule secretion starts before the establishment of tight junction barrier for paracellular tracers in mammalian epidermis. PLoS One 7:e31641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Jakasa I, De Jongh CM, Verberk MM, Bos JD, Kežić S (2006) Percutaneous penetration of sodium lauryl sulphate is increased in uninvolved skin of patients with atopic dermatitis compared with control subjects. Brit J Dermatol 155:104–109

    Article  CAS  Google Scholar 

  53. Jakasa I, Verberk MM, Esposito M, Bos JD, Kezic S (2007) Altered penetration of polyethylene glycols into uninvolved skin of atopic dermatitis patients. J Invest Dermatol 127:129–134

    Article  CAS  PubMed  Google Scholar 

  54. Janssens M, van Smeden J, Gooris GS, Bras W, Portale G, Caspers PJ, Vreeken RJ, Hankemeier T, Kezic S, Wolterbeek R, Lavrijsen AP, Bouwstra JA (2012) Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients. J Lipid Res 53:2755–2766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Jin S-P, Han SB, Kim YK, Park EE, Doh EJ, Kim KH, Lee DH, and Chung, JH (2016) Changes in tight junction protein expression in intrinsic aging and photoaging in human skin in vivo. J Dermatol Sci

  56. Johnson-Henry KC, Donato KA, Shen-Tu G, Gordanpour M, Sherman PM (2008) Lactobacillus rhamnosus strain GG prevents enterohemorrhagic Escherichia coli O157:H7-induced changes in epithelial barrier function. Infect Immun 76:1340–1348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Jung EG, Augustin M, Bahmer FA, Bahmer JA, Bayerl C, Boonen HPJ, Coors E, Fischer M, Grimmel M, Hadshiew I, Hauswirth U, Hofmann H, Jung EG, Kimmig W, Knußmann-Hartig E, Köberle M, Kohrmeyer K, Meissner M, Miller X, Moll I, Radtke M-A, Rauterberg A, Rose C, Schoch D, Schulze W, Siemann-Harms U, Stangl S, Tsianakas A, Varwig-Janßen D, Voigtländer V, Weiß J, Weßbecher R, Witte J (2016) Dermatologie. Georg Thieme Verlag, Stuttgart

    Google Scholar 

  58. Jungersted JM, Scheer H, Mempel M, Baurecht H, Cifuentes L, Høgh JK, Hellgren LI, Jemec GBE, Agner T, Weidinger S (2010) Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema. Allergy 65:911–918

    Article  CAS  PubMed  Google Scholar 

  59. Kaplan DH, Igyártó BZ, Gaspari AA (2012) Early immune events in the induction of allergic contact dermatitis. Nat Rev Immunol 12:114–124

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Kawada C, Hasegawa T, Watanabe M, Nomura Y (2013) Dietary glucosylceramide enhances tight junction function in skin epidermis via induction of claudin-1. Biosci Biotechnol Biochem 77:867–869

    Article  CAS  PubMed  Google Scholar 

  61. Kawasaki H, Nagao K, Kubo A, Hata T, Shimizu A, Mizuno H, Yamada T, Amagai M (2012) Altered stratum corneum barrier and enhanced percutaneous immune responses in filaggrin-null mice. J Allergy Clin Immunol 129:1538–1546 e1536

    Article  CAS  PubMed  Google Scholar 

  62. Kiatsurayanon C, Niyonsaba F, Smithrithee R, Akiyama T, Ushio H, Hara M, Okumura K, Ikeda S, Ogawa H (2014) Host defense (antimicrobial) peptide, human beta-defensin-3, improves the function of the epithelial tight-junction barrier in human keratinocytes. J Invest Dermatol 134:2163–2173

    Article  CAS  PubMed  Google Scholar 

  63. Kirchmeier P, Sayar E, Hotz A, Hausser I, Islek A, Yilmaz A, Artan R, Fischer J (2014) Novel mutation in the CLDN1 gene in a Turkish family with neonatal ichthyosis sclerosing cholangitis (NISCH) syndrome. The British journal of dermatology 170:976–978

    Article  CAS  PubMed  Google Scholar 

  64. Kirschner N, Brandner JM (2012) Barriers and more: functions of tight junction proteins in the skin. Ann N Y Acad Sci 1257:158–166

    Article  CAS  PubMed  Google Scholar 

  65. Kirschner N, Houdek P, Fromm M, Moll I, Brandner JM (2010) Tight junctions form a barrier in human epidermis. Eur J Cell Biol 89:839–842

    Article  CAS  PubMed  Google Scholar 

  66. Kirschner N, Poetzl C, von den Driesch P, Wladykowski E, Moll I, Behne MJ, Brandner JM (2009) Alteration of tight junction proteins is an early event in psoriasis: putative involvement of proinflammatory cytokines. Am J Pathol 175:1095–1106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kirschner N, Rosenthal R, Furuse M, Moll I, Fromm M, Brandner JM (2013) Contribution of tight junction proteins to ion, macromolecule, and water barrier in keratinocytes. J Invest Dermatol 133:1161–1169

    Article  CAS  PubMed  Google Scholar 

  68. Köllisch G, Kalali BN, Voelcker V, Wallich R, Behrendt H, Ring J, Bauer S, Jakob T, Mempel M, Ollert M (2005) Various members of the toll-like receptor family contribute to the innate immune response of human epidermal keratinocytes. Immunology 114:531–541

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Kong HH, J O, Deming C, Conlan S, Gricem EA, Beatson MA, Nomicos E, Polley EC, Komarow HD, Program NCS, Murray PR, Turner ML, Segre JA (2012) Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res 22:850–859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Koppes SA, Engebretsen K, Clausen ML, Jakasa I, Knykin D, Brans R, Tončic RJ, Molin S, Puppels G, Riethmüller C, Berents T, Oivind Holm J, Suomela S, Hummler E, Brandner J, Angelova-Fischer I, Agner T, Thierse H-J, John SM, Kezic S, Martin SF, and Thyssen JP. Biomarkers for allergic contact dermatitis and methods to determine them submitted

  71. Kubo A, Nagao K, Amagai M (2012) Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases. J Clin Invest 122:440–447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kubo A, Nagao K, Yokouchi M, Sasaki H, Amagai M (2009) External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers. J Exp Med 206:2937–2946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kubo T, Sugimoto K, Kojima T, Sawada N, Sato N, Ichimiya S (2014) Tight junction protein claudin-4 is modulated via DeltaNp63 in human keratinocytes. Biochem Biophys Res Commun 455:205–211

    Article  CAS  PubMed  Google Scholar 

  74. Kuo IH, Carpenter-Mendini A, Yoshida T, McGirt LY, Ivanov AI, Barnes KC, Gallo RL, Borkowski AW, Yamasaki K, Leung DY, Georas SN, De Benedetto A, Beck LA (2013) Activation of epidermal toll-like receptor 2 enhances tight junction function: implications for atopic dermatitis and skin barrier repair. J Invest Dermatol 133:988–998

    Article  CAS  PubMed  Google Scholar 

  75. Kuo IH, Yoshida T, De Benedetto A, Beck LA (2013) The cutaneous innate immune response in patients with atopic dermatitis. J Aller Clin Immunol 131:266–278

    Article  CAS  Google Scholar 

  76. Langbein L, Pape U-F, Grund C, Kuhn C, Praetzel S, Moll I, Moll R, Franke WW (2003) Tight junction-related strucutres in the absence of a lumen: occludin claudins and tight junction plaque proteins in densely packed cell formations of stratified epithalia and squamous cell carcinomas. Eur J Cell Biol 82:385–400

    Article  CAS  PubMed  Google Scholar 

  77. Lee CH, Chuang HY, Shih CC, Jong SB, Chang CH, Yu HS (2006) Transepidermal water loss, serum IgE and β-endorphin as important and independent biological markers for development of itch intensity in atopic dermatitis. Brit J Dermatol 154:1100–1107

    Article  CAS  Google Scholar 

  78. Leung DYM, Boguniewicz M, Howell MD, Nomura I, Hamid QA (2004) New insights into atopic dermatitis. J Clin Invest 113:651–657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Martin SF (2012) Contact dermatitis: from pathomechanisms to immunotoxicology. Exp Dermatol 21:382–389

    Article  CAS  PubMed  Google Scholar 

  80. Martin SF (2015) New concepts in cutaneous allergy. Contact Dermatitis 72:2–10

    Article  PubMed  Google Scholar 

  81. Medigeshi GR, Hirsch AJ, Brien JD, Uhrlaub JL, Mason PW, Wiley C, Nikolich-Zugich J, Nelson JA (2009) West Nile virus capsid degradation of claudin proteins disrupts epithelial barrier function. J Virol 83:6125–6134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Midorikawa K, Ouhara K, Komatsuzawa H, Kawai T, Yamada S, Fujiwara T, Yamazaki K, Sayama K, Taubman MA, Kurihara H, Hashimoto K, Sugai M (2003) Staphylococcus aureus Susceptibility to innate antimicrobial peptides, β-defensins and CAP18. Expressed by Human Keratinocytes Infect Immun 71:3730–3739

  83. Miller LS, Cho JS (2011) Immunity against Staphylococcus aureus cutaneous infections. Nat Rev Immunol 11:505–518

    Article  CAS  PubMed  Google Scholar 

  84. Mills KJ, P H, Henry J, Tamura M, JP T, J X (2012) Dandruff/seborrhoeic dermatitis is characterized by an inflammatory genomic signature and possible immune dysfunction: transcriptional analysis of the condition and treatment effects of zinc pyrithione. Brit J Dermatol 166:33–40

    Article  CAS  Google Scholar 

  85. Moll I (2016) Dermatologie. Thieme, Stuttgart

    Book  Google Scholar 

  86. Morita K, Itoh M, Saitou M, Ando-Akatsuka Y, Furuse M, Yoneda K, Imamura S, Fujimoto K, Tsukita S (1998) Subcellular distribution of tight junction-associated proteins (occludin, ZO-1, ZO-2) in rodent skin. J Invest Dermatol 110:862–866

    Article  CAS  PubMed  Google Scholar 

  87. Nakajima M, Nagase S, Iida M, Takeda S, Yamashita M, Watari A, Shirasago Y, Fukasawa M, Takeda H, Sawasaki T, Yagi K, Kondoh M (2015) Claudin-1 binder enhances epidermal permeability in a human keratinocyte model. J Pharmacol Exp Ther 354:440–447

    Article  CAS  PubMed  Google Scholar 

  88. Niehues H, Schalkwijk J, van Vlijmen-Willems IM, Rodijk-Olthuis D, van Rossum MM, Wladykowski E, Brandner JM, van den Bogaard EH, and Zeeuwen PL (2016) Epidermal equivalents of filaggrin null keratinocytes do not show impaired skin barrier function. J Allergy Clin Immunol

  89. O’Neill CA, Garrod D (2011) Tight junction proteins and the epidermis. Exp Dermatol 20:88–91

    Article  PubMed  CAS  Google Scholar 

  90. Ohnemus U, Kohrmeyer K, Houdek P, Rohde H, Wladykowski E, Vidal S, Horstkotte MA, Aepfelbacher M, Kirschner N, Behne MJ, Moll I, Brandner JM (2008) Regulation of epidermal tight-junctions (TJ) during infection with exfoliative toxin-negative Staphylococcus strains. J Invest Dermatol 128:906–916

    Article  CAS  PubMed  Google Scholar 

  91. Olivry T, Dunston SM (2015) Expression patterns of superficial epidermal adhesion molecules in an experimental dog model of acute atopic dermatitis skin lesions. Vet Dermatol 26:53–56 e-17-58

    Article  PubMed  Google Scholar 

  92. Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, Goudie DR, Sandilands A, Campbell LE, Smith FJ, O’Regan GM, Watson RM, Cecil JE, Bale SJ, Compton JG, DiGiovanna JJ, Fleckman P, Lewis-Jones S, Arseculeratne G, Sergeant A, Munro CS, El Houate B, McElreavey K, Halkjaer LB, Bisgaard H, Mukhopadhyay S, McLean WH (2006) Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38:441–446

    Article  CAS  PubMed  Google Scholar 

  93. Peltonen S, Riehokainen J, Pummi K, Peltonen J (2007) Tight junction components occludin, ZO-1, and claudin-1, -4 and -5 in active and healing psoriasis. The British journal of dermatology 156:466–472

    Article  CAS  PubMed  Google Scholar 

  94. Piche T (2014) Tight junctions and IBS—the link between epithelial permeability, low-grade inflammation, and symptom generation? Neurogastroenterol Motil 26:296–302

    Article  CAS  PubMed  Google Scholar 

  95. Proksch E, Brandner JM, Jensen JM (2008) The skin: an indispensable barrier. Exp Dermatol 17:1063–1072

    Article  PubMed  Google Scholar 

  96. Proksch E, Folster-Holst R, Jensen JM (2006) Skin barrier function, epidermal proliferation and differentiation in eczema. J Dermatol Sci 43:159–169

    Article  CAS  PubMed  Google Scholar 

  97. Pummi K, Malminen M, Aho H, Karvonen S-L, Peltonen J, Peltonen S (2001) Epidermal tight junctions: ZO-1 and occludin are expressed in mature, developing, and affected skin and in vitro differentiating keratinocytes. J Invest Dermatol 117:1050–1058

    Article  CAS  PubMed  Google Scholar 

  98. Rachow S, Zorn-Kruppa M, Ohnemus U, Kirschner N, Vidal-y-Sy S, von den Driesch P, Bornchen C, Eberle J, Mildner M, Vettorazzi E, Rosenthal R, Moll I, Brandner JM (2013) Occludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis. PLoS One 8:e55116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Rassner G (2009) Dermatologie : Lehrbuch und Atlas (Dermatology, textbook and atlas). München, Elsevier, Urban & Fischer

    Google Scholar 

  100. Röhl M, Tjernlund A, Mehta SD, Pettersson P, Bailey RC, and Broliden K (2015) Comparable mRNA expression of inflammatory markers but lower claudin-1 mRNA levels in foreskin tissue of HSV-2 seropositive versus seronegative asymptomatic Kenyan young men. BMJ Open 5

  101. Ross-Hansen K, Linneberg A, Johansen JD, Hersoug LG, Brasch-Andersen C, Menne T, Thyssen JP (2013) The role of glutathione S-transferase and claudin-1 gene polymorphisms in contact sensitization: a cross-sectional study. The British journal of dermatology 168:762–770

    Article  CAS  PubMed  Google Scholar 

  102. Rothman PF (1944) The physiology of the skin. Ann Rev Physiol 6:195–224

    Article  CAS  Google Scholar 

  103. Rustemeyer T, van Hoogstraten IM, von Blomberg BME, Gibbs S, and Scheper RJ (2011) Mechanisms of irritant and allergic contact dermatitis. In: Contact dermatitis. Springer p. 43–90

  104. Sator P-G, Schmidt JB, Hönigsmann H (2003) Comparison of epidermal hydration and skin surface lipids in healthy individuals and in patients with atopic dermatitis. J Am Acad Dermatol 48:352–358

    Article  PubMed  Google Scholar 

  105. Schwartz JR, Messenger AG, Tosti A, Todd G, Hordinsky M, Hay RJ, Wang X, Zachariae C, Kerr KM, Henry JP, Rust RC, Robinson MK (2013) A comprehensive pathophysiology of dandruff and seborrheic dermatitis – towards a more precise definition of scalp health. Acta Derm Venereol 93:131–137

    Article  CAS  PubMed  Google Scholar 

  106. Seguchi T, Chang-Yi C, Kusuda S, Takahashi M, Aisu K, Tezuka T (1996) Decreased expression of filaggrin in atopic skin. Arch Dermatol Res 288:442–446

    Article  CAS  PubMed  Google Scholar 

  107. Shaker M (2014) New insights into the allergic march. Curr Opin Pediatr 26:516–520

    Article  PubMed  Google Scholar 

  108. Sieprawska-Lupa M, Mydel P, Krawczyk K, Wójcik K, Puklo M, Lupa B, Suder P, Silberring J, Reed M, Pohl J, Shafer W, McAleese F, Foster T, Travis J, Potempa J (2004) Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. Antimicrob Agents Ch 48:4673–4679

    Article  CAS  Google Scholar 

  109. Soyka MB, Wawrzyniak P, Eiwegger T, Holzmann D, Treis A, Wanke K, Kast JI, Akdis CA (2012) Defective epithelial barrier in chronic rhinosinusitis: the regulation of tight junctions by IFN-γ and IL-4. J Aller Clin Immunol 130:1087–1096.e1010

    Article  CAS  Google Scholar 

  110. Suarez-Farinas M, Ungar B, Correa da Rosa J, Ewald DA, Rozenblit M, Gonzalez J, H X, Zheng X, Peng X, Estrada YD, Dillon SR, Krueger JG, Guttman-Yassky E (2015) RNA sequencing atopic dermatitis transcriptome profiling provides insights into novel disease mechanisms with potential therapeutic implications. J Allergy Clin Immunol 135:1218–1227

    Article  CAS  PubMed  Google Scholar 

  111. Sugawara T, Iwamoto N, Akashi M, Kojima T, Hisatsune J, Sugai M, Furuse M (2013) Tight junction dysfunction in the stratum granulosum leads to aberrant stratum corneum barrier function in claudin-1-deficient mice. J Dermatol Sci 70:12–18

    Article  CAS  PubMed  Google Scholar 

  112. Sultana R, McBain AJ, O’Neill CA (2013) Strain-dependent augmentation of tight-junction barrier function in human primary epidermal keratinocytes by Lactobacillus and Bifidobacterium lysates. Appl Environ Microb 79:4887–4894

    Article  CAS  Google Scholar 

  113. Sumitomo T, Nakata M, Higashino M, Yamaguchi M, Kawabata S (2016) Group A Streptococcus exploits human plasminogen for bacterial translocation across epithelial barrier via tricellular tight junctions. Scientific Reports 7:20069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Tokumasu R, Yamaga K, Yamazaki Y, Murota H, Suzuki K, Tamura A, Bando K, Furuta Y, Katayama I, Tsukita S (2016) Dose-dependent role of claudin-1 in vivo in orchestrating features of atopic dermatitis. Proc Natl Acad Sci U S A 113:E4061–E4068

    Article  CAS  PubMed  Google Scholar 

  115. Troy TC, Arabzadeh A, Lariviere NM, Enikanolaiye A, Turksen K (2009) Dermatitis and aging-related barrier dysfunction in transgenic mice overexpressing an epidermal-targeted claudin 6 tail deletion mutant. PLoS One 4:e7814

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Tunggal JA, Helfrich I, Schmitz A, Schwarz H, Gunzel D, Fromm M, Kemler R, Krieg T, Niessen CM (2005) E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions. EMBO J 24:1146–1156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Turksen K, Troy TC (2002) Permeability barrier dysfunction in transgenic mice overexpressing claudin 6. Development 129:1775–1784

    CAS  PubMed  Google Scholar 

  118. Ulluwishewa D, Anderson RC, McNabb WC, Moughan PJ, Wells JM, Roy NC (2011) Regulation of tight junction permeability by intestinal bacteria and dietary components. J Nutr 141:769–776

    Article  CAS  PubMed  Google Scholar 

  119. van Smeden J, Janssens M, Kaye ECJ, Caspers PJ, Lavrijsen AP, Vreeken RJ, Bouwstra JA (2014) The importance of free fatty acid chain length for the skin barrier function in atopic eczema patients. Exp Dermatol 23:45–52

    Article  PubMed  CAS  Google Scholar 

  120. Watson RE, Poddar R, Walker JM, McGuill I, Hoare LM, Griffiths CE, O’Neill CA (2007) Altered claudin expression is a feature of chronic plaque psoriasis. J Pathol 212:450–458

    Article  CAS  PubMed  Google Scholar 

  121. Werfel T, Allam J-P, Biedermann T, Eyerich K, Gilles S, Guttman-Yassky E, Hoetzenecker W, Knol E, Simon H-U, Wollenberg A, Bieber T, Lauener R, Schmid-Grendelmeier P, Traidl-Hoffmann C, Akdis CA (2016) Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Aller Clin Immunol 138:336–349

    Article  CAS  Google Scholar 

  122. Winge MCG, Bilcha KD, Liedén A, Shibeshi D, Sandilands A, Wahlgren CF, McLean WHI, Nordenskjöld M, Bradley M (2011) Novel filaggrin mutation but no other loss-of-function variants found in Ethiopian patients with atopic dermatitis. Brit J Dermatol 165:1074–1080

    Article  CAS  Google Scholar 

  123. Wolff K, Johnson RA, Suurmond D (2005) Fitzpatrick’s color atlas & synopsis of clinical dermatology. McGraw-Hill, New York City

    Google Scholar 

  124. Woo YR, Lim JH, Cho DH, and Park HJ (2016) Rosacea: molecular mechanisms and management of a chronic cutaneous inflammatory condition. Int J Mol Sci 17

  125. Yamamoto T, Kurasawa M, Hattori T, Maeda T, Nakano H, Sasaki H (2008) Relationship between expression of tight junction-related molecules and perturbed epidermal barrier function in UVB-irradiated hairless mice. Arch Dermatol Res 300:61–68

    Article  CAS  PubMed  Google Scholar 

  126. Yokouchi M, Kubo A, Kawasaki H, Yoshida K, Ishii K, Furuse M, Amagai M (2015) Epidermal tight junction barrier function is altered by skin inflammation, but not by filaggrin-deficient stratum corneum. J Dermatol Sci 77:28–36

    Article  CAS  PubMed  Google Scholar 

  127. Yoshida K, Kubo A, Fujita H, Yokouchi M, Ishii K, Kawasaki H, Nomura T, Shimizu H, Kouyama K, Ebihara T, Nagao K, Amagai M (2014) Distinct behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight junctions in patients with atopic dermatitis. J Allergy Clin Immunol 134:856–864

    Article  PubMed  Google Scholar 

  128. Yoshida K, Yokouchi M, Nagao K, Ishii K, Amagai M, Kubo A (2013) Functional tight junction barrier localizes in the second layer of the stratum granulosum of human epidermis. J Dermatol Sci 71:89–99

    Article  PubMed  Google Scholar 

  129. Yu HS, Kang MJ, Kwon JW, Lee SY, Lee E, Yang SI, Jung YH, Hong K, Kim YJ, Lee SH, Kim HJ, Kim HY, Seo JH, Kim BJ, Kim HB, Hong SJ (2015) Claudin-1 polymorphism modifies the effect of mold exposure on the development of atopic dermatitis and production of IgE. J Allergy Clin Immunol 135:827–830 e825

    Article  CAS  PubMed  Google Scholar 

  130. Yuki T, Hachiya A, Kusaka A, Sriwiriyanont P, Visscher MO, Morita K, Muto M, Miyachi Y, Sugiyama Y, Inoue S (2011) Characterization of tight junctions and their disruption by UVB in human epidermis and cultured keratinocytes. J Invest Dermatol 131:744–752

    Article  CAS  PubMed  Google Scholar 

  131. Yuki T, Haratake A, Koishikawa H, Morita K, Miyachi Y, Inoue S (2007) Tight junction proteins in keratinocytes: localization and contribution to barrier function. Exp Dermatol 16:324–330

    Article  CAS  PubMed  Google Scholar 

  132. Yuki T, Komiya A, Kusaka A, Kuze T, Sugiyama Y, Inoue S (2013) Impaired tight junctions obstruct stratum corneum formation by altering polar lipid and profilaggrin processing. J Dermatol Sci 69:148–158

    Article  CAS  PubMed  Google Scholar 

  133. Yuki T, Tobiishi M, Kusaka-Kikushima A, Ota Y, Tokura Y (2016) Impaired tight junctions in atopic dermatitis skin and in a skin-equivalent model treated with interleukin-17. PLoS One 11:e0161759

    Article  PubMed  PubMed Central  Google Scholar 

  134. Yuki T, Yoshida H, Akazawa Y, Komiya A, Sugiyama Y, Inoue S (2011) Activation of TLR2 enhances tight junction barrier in epidermal keratinocytes. J Immunol 187:3230–3237

    Article  CAS  PubMed  Google Scholar 

  135. Zimmerli SC, Hauser C (2007) Langerhans cells and lymph node dendritic cells express the tight junction component claudin-1. J Invest Dermatol 127:2381–2390

    Article  CAS  PubMed  Google Scholar 

  136. Zimmerli SC, Kerl K, Hadj-Rabia S, Hohl D, Hauser C (2008) Human epidermal Langerhans cells express the tight junction protein claudin-1 and are present in human genetic claudin-1 deficiency (NISCH syndrome). Exp Dermatol 17:20–23

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Sabine Vidal-y-Sy and Claudia Bohner for technical and scientific assistance.

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  1. Department of Dermatology and Venerology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Katja Bäsler & Johanna M. Brandner

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  1. Katja Bäsler
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Correspondence to Johanna M. Brandner.

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This work was supported by the Deutsche Forschungsgemeinschaft (BR 1982/4-1 to JMB).

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This article is published as part of the special issue on tight junctions (European Journal of Physiology).

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Bäsler, K., Brandner, J.M. Tight junctions in skin inflammation. Pflugers Arch - Eur J Physiol 469, 3–14 (2017). https://doi.org/10.1007/s00424-016-1903-9

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