Skin Barrier Function in Atopic Dermatitis

  • Hiroyuki MurotaEmail author
  • Kosuke Yamaga
  • Ichiro Katayama


Recent approaches to explore the pathogenic etiologies of atopic dermatitis using molecular genetic techniques have revealed underlying abnormalities in skin barrier function. Primary cutaneous barrier function is maintained by several physiological factors, including proper skin permeability that is regulated by both the stratum corneum barrier and the tight junction barrier and innate immune response of secretion from both the skin and skin appendages. The corneocyte lipid envelope and natural moisturizing factors derived from filaggrin prevent skin dryness and function in pathogen control. Epidermal tight junctions are composed of claudin-1, which comprises a water barrier correlated with its expression level. Secretions, such as sebum and sweat, contribute to decrease the impact of environmental stimuli (e.g., antigens, detergents, proteases, heat, and mechanical stimuli) to maintain the moistness of the stratum corneum and to regulate temperature. Disruption or dysfunction of these mechanisms impairs skin homeostasis and allows the invasion of pathogens from outside. Development of internal inflammation causes external barrier disruption in turn. This vicious cycle contributes to the chronic inflammation of atopic dermatitis. Appropriate guidance with a main focus on barrier restoration will restrain recurrence of the symptoms. This chapter reviews the barrier function of skin in atopic dermatitis.


Atopic dermatitis Barrier Filaggrin Tight junction Claudins Stratum corneum Anti-microbial peptides Corneocyte lipid envelope 


Conflict of Interest

The authors have no conflicts of interest to declare.


  1. 1.
    Proksch E, Folster-Holst R, Jensen JM. Skin barrier function, epidermal proliferation and differentiation in eczema. J Dermatol Sci. 2006;43:159–69.CrossRefPubMedGoogle Scholar
  2. 2.
    Seidenari S, Girusti G. Objective assessment of the skin of child affected by atopic dermatitis: a study of pH, capacitance and TEWL in eczematous and clinically uninvolved skin. Acta Derm Venereol. 1995;75(6):429–33.PubMedGoogle Scholar
  3. 3.
    Grimalt R, Mengeaud V, Cambazard F. The steroid-sparing effect of an emollient therapy in infants with atopic dermatitis: a randomized controlled study. Dermatology. 2007;214:61–7.CrossRefPubMedGoogle Scholar
  4. 4.
    Murota H, Takahashi A, Nishioka M, et al. Showering reduces atopic dermatitis in elementary school students. Eur J Dermatol. 2010;20:410–1.PubMedGoogle Scholar
  5. 5.
    Elias PM, Wood LC, Freingold KR. Epidermal pathogenesis of inflammatory dermatoses. Am J Contact Dermat. 1999;10:119–26.PubMedGoogle Scholar
  6. 6.
    Elias PM. Stratum corneum as an innate immune element. Semin Immunopathol. 2007;29:3–14.CrossRefPubMedGoogle Scholar
  7. 7.
    Elias PM. Stratum corneum defensive functions: an integrated view. J Invest Dermatol. 2005;125:183–200.CrossRefPubMedGoogle Scholar
  8. 8.
    Walley AJ, Chanvanas S, Moffatt MF, et al. Gene polymorphism in Netherton and common atopic disease. Nat Genet. 2001;29:175–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Elias PM, Schmutt M. Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Curr Opin Allergy Clin Immunol. 2009;9:437–46.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Saeki H, Nakahara T, Tanaka A, Kabashima K, Sugaya M, Murota H, Ebihara T, Kataoka Y, Aihara M, Etoh T, Katoh N, Committee for Clinical Practice Guidelines for the Management of Atopic Dermatitis of Japanese Dermatological Association. Clinical practice guidelines for the management of atopic dermatitis 2016. J Dermatol. 2016;43:1117–45.CrossRefPubMedGoogle Scholar
  11. 11.
    Hachem JP, Houben E, Crumrine D, et al. Serine protease signaling of epidermal permeability barrier homeostasis. J Invest Dermatol. 2006;126:2074–86.CrossRefPubMedGoogle Scholar
  12. 12.
    Fleckman P, Brumbaugh S. Absence of the granular layer and keratohyalin define a morphologically distinct subset of individuals with ichthyosis vulgaris. Exp Dermatol. 2002;11:327–36.CrossRefPubMedGoogle Scholar
  13. 13.
    Kono M, Nomura T, Ohguchi Y, Mizuno O, Suzuki S, Tsujiuchi H, Hamajima N, McLean WH, Shimizu H, Akiyama M. Comprehensive screening for a complete set of Japanese-population-specific filaggrin gene mutations. Allergy. 2014;69:537–40.CrossRefPubMedGoogle Scholar
  14. 14.
    Egawa G, Kabashima K. Multifactorial skin barrier deficiency and atopic dermatitis: essential topics to prevent the atopic march. J Allergy Clin Immunol. 2016;138:350–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Tamura A, Tsukita S. Paracellular barrier and channel functions of TJ claudins in organizing biological systems: advances in the field of barriology revealed in knockout mice. Semin Cell Dev Biol. 2014;36:177–85.CrossRefPubMedGoogle Scholar
  16. 16.
    Kubo A, Nagao K, Yokouchi M, Sasaki H, Amagai M. External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers. J Exp Med. 2009;206:2937–46.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Furuse M, et al. Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol. 2002;156:1099–111.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Sugawara T, et al. Tight junction dysfunction in the stratum granulosum leads to aberrant stratum corneum barrier function in claudin-1-deficient mice. J Dermatol Sci. 2013;70:12–8.CrossRefPubMedGoogle Scholar
  19. 19.
    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. Reductions in claudin-1 may enhance susceptibility to herpes simplex virus 1infections in atopic dermatitis. J Allergy Clin Immunol. 2011;128:242–6.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    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. Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol. 2011;127:773–86.CrossRefPubMedGoogle Scholar
  21. 21.
    Tokumasu R, Yamaga K, Yamazaki Y, Murota H, Suzuki K, Tamura A, Bando K, Furuta Y, Katayama I, Tsukita S. Dose-dependent role of claudin-1 in vivo in orchestrating features of atopic dermatitis. Proc Natl Acad Sci U S A. 2016;113(28):E4061–8.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Totté JE, van der Feltz WT, Hennekam M, van Belkum A, van Zuuren EJ, Pasmans SG. Prevalence and odds of Staphylococcus aureus carriage in atopic dermatitis: a systematic review and meta-analysis. Br J Dermatol. 2016;175:687–95.CrossRefPubMedGoogle Scholar
  23. 23.
    McGirt LY, Beck LA. Innate immune defects in atopic dermatitis. J Allergy Clin Immunol. 2006;118:202–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Medzhitov R, Janeway C Jr. Innate immunity. N Engl J Med. 2000;343:338–44.CrossRefPubMedGoogle Scholar
  25. 25.
    Esche C, Stellato C, Beck LA. Chemokines: key players in innate and adaptive immunity. J Invest Dermatol. 2005;125:615–28.CrossRefPubMedGoogle Scholar
  26. 26.
    Murota H, Matsui S, Ono E, Kijima A, Kikuta J, Ishii M, Katayama I. Sweat, the driving force behind normal skin: an emerging perspective on functional biology and regulatory mechanisms. J Dermatol Sci. 2015;77(1):3–10.CrossRefPubMedGoogle Scholar
  27. 27.
    Rieg S, Saborowski V, Kern WV, Jonas D, Bruckner-Tuderman L, Hofmann SC. Expression of the sweat-derived innate defence antimicrobial peptide dermcidin is not impaired in Staphylococcus aureus colonization or recurrent skin infections. Clin Exp Dermatol. 2014;39(2):209–12.CrossRefPubMedGoogle Scholar
  28. 28.
    Terao M, Murota H, Kimura A, Kato A, Ishikawa A, Igawa K, Miyoshi E, Katayama I. 11β-Hydroxysteroid dehydrogenase-1 is a novel regulator of skin homeostasis and a candidate target for promoting tissue repair. PLoS One. 2011;6:e25039.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Itoi S, Terao M, Murota H, Katayama I. 11β-Hydroxysteroid dehydrogenase 1 contributes to the pro-inflammatory response of keratinocytes. Biochem Biophys Res Commun. 2013;440:265–70.CrossRefPubMedGoogle Scholar
  30. 30.
    Terao M, Itoi S, Matsumura S, Yang L, Murota H, Katayama I. Local glucocorticoid activation by 11β-Hydroxysteroid dehydrogenase 1 in keratinocytes: the role in Hapten-induced dermatitis. Am J Pathol. 2016;186:1499–510.CrossRefPubMedGoogle Scholar
  31. 31.
    Itoi-Ochi S, Terao M, Murota H, Katayama I. Local corticosterone activation by 11β-hydroxysteroid dehydrogenase 1 in keratinocytes: the role in narrow-band UVB-induced dermatitis. Dermatoendocrinol. 2016;8(1):e1119958.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Terao M, Katayama I. Local cortisol/corticosterone activation in skin physiology and pathology. J Dermatol Sci. 2016;84(1):11–6.CrossRefPubMedGoogle Scholar
  33. 33.
    Murota H, Itoi S, Terao M, Matsui S, Kawai H, Satou Y, Suda K, Katayama I. Topical cholesterol treatment ameliorates hapten-evoked cutaneous hypersensitivity by sustaining expression of 11β-HSD1 in epidermis. Exp Dermatol. 2014;23:68–70.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Hiroyuki Murota
    • 1
    Email author
  • Kosuke Yamaga
    • 1
  • Ichiro Katayama
    • 1
  1. 1.Dermatology, Department of Integrated Medicine, Graduate School of MedicineOsaka UniversityOsaka 565-0871Japan

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