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Pathogenesis of atopic dermatitis: New developments

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Abstract

Atopic dermatitis (AD) is a paradigmatic skin disease in which multiple gene-gene and gene-environment interactions play a pivotal role. Although the complex pathophysiologic network of AD explains the large spectrum of risk and trigger factors, it is far from being comprehensively understood. Hence, genetic modifications underlying the dysfunction of the epidermal skin barrier as well as the close interaction of innate and adaptive immune mechanisms were the focus of intensive research studies. This review aims to summarize the most recent findings in this field.

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References and Recommended Reading

  1. Palmer CN, Irvine AD, Terron-Kwiatkowski A, et al.: Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006, 38:441–446.

    Article  PubMed  CAS  Google Scholar 

  2. Baurecht H, Irvine AD, Novak N, et al.: Toward a major risk factor for atopic eczema: meta-analysis of filaggrin polymorphism data. J Allergy Clin Immunol 2007, 120:1406–1412.

    Article  PubMed  CAS  Google Scholar 

  3. Weidinger S, Illig T, Baurecht H, et al.: Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol 2006, 118:214–219.

    Article  PubMed  CAS  Google Scholar 

  4. Weidinger S, Rodriguez E, Stahl C, et al.: Filaggrin mutations strongly predispose to early-onset and extrinsic atopic dermatitis. J Invest Dermatol 2007, 127:724–726.

    Article  PubMed  CAS  Google Scholar 

  5. Bisgaard H, Simpson A, Palmer CN, et al.: Gene-environment interaction in the onset of eczema in infancy: filaggrin loss-of-function mutations enhanced by neonatal cat exposure. PLoS Med 2008, 5:e131.

    Article  PubMed  CAS  Google Scholar 

  6. Kezic S, Kemperman PM, Koster ES, et al.: Loss-of-function mutations in the filaggrin gene lead to reduced level of natural moisturizing factor in the stratum corneum. J Invest Dermatol 2008, 128:2117–2119.

    Article  PubMed  CAS  Google Scholar 

  7. de Jongh CM, Khrenova L, Verberk MM, et al.: Loss-of-function polymorphisms in the filaggrin gene are associated with an increased susceptibility to chronic irritant contact dermatitis: a case-control study. Br J Dermatol 2008, 159:621–627.

    Article  PubMed  CAS  Google Scholar 

  8. Novak N, Baurecht H, Schafer T, et al.: Loss-of-function mutations in the filaggrin gene and allergic contact sensitization to nickel. J Invest Dermatol 2008, 128:1430–1435.

    Article  PubMed  CAS  Google Scholar 

  9. Howell MD, Kim BE, Gao P, et al.: Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol 2007, 120:150–155.

    Article  PubMed  CAS  Google Scholar 

  10. Cookson W: The immunogenetics of asthma and eczema: a new focus on the epithelium. Nat Rev Immunol 2004, 4:978–988.

    Article  PubMed  CAS  Google Scholar 

  11. Vasilopoulos Y, Cork MJ, Murphy R, et al.: Genetic association between an AACC insertion in the 3’UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis. J Invest Dermatol 2004, 123:62–66.

    Article  PubMed  CAS  Google Scholar 

  12. De Benedetto A, Latchney LE, McGirt LS, et al.: The tight junction protein Claudin-1 is dysregulated in atopic dermatitis. J Allergy Clin Immunol 2008, 121:S32.

    Article  Google Scholar 

  13. Soderhall C, Marenholz I, Kerscher T, et al.: Variants in a novel epidermal collagen gene (COL29A1) are associated with atopic dermatitis. PLoS Biol 2007, 5:e242.

    Article  PubMed  CAS  Google Scholar 

  14. Esparza-Gordillo J, Weidinger S, Fölster-Holst R, et al.: A common variant on chromosome 11q13 is associated with atopic dermatitis. Nat Genet 2009, 41:596–601.

    Article  PubMed  CAS  Google Scholar 

  15. Hata TR, Gallo RL: Antimicrobial peptides, skin infections, and atopic dermatitis. Semin Cutan Med Surg 2008, 27:144–150.

    Article  PubMed  CAS  Google Scholar 

  16. Maintz L, Novak N: Getting more and more complex: The pathophysiology of atopic eczema. Eur J Dermatol 2007, 17:267–283.

    PubMed  CAS  Google Scholar 

  17. Ahmad-Nejad P, Mrabet-Dahbi S, Breuer K, et al.: The Toll-like receptor 2 R753Q polymorphism defines a subgroup of patients with atopic dermatitis having severe phenotype. J Allergy Clin Immunol 2004, 113:565–567.

    Article  PubMed  CAS  Google Scholar 

  18. Weidinger S, Novak N, Klopp N, et al.: Lack of association between Toll-like receptor 2 and Toll-like receptor 4 polymorphisms and atopic eczema. J Allergy Clin Immunol 2006, 118:277–279.

    Article  PubMed  CAS  Google Scholar 

  19. Niebuhr M, Langnickel J, Draing C, et al.: Dysregulation of Toll-like receptor-2 (TLR-2)-induced effects in monocytes from patients with atopic dermatitis: impact of the TLR-2 R753Q polymorphism. Allergy 2008, 63:728–734.

    Article  PubMed  CAS  Google Scholar 

  20. Novak N, Yu CF, Bussmann C, et al.: Putative association of a TLR9 promoter polymorphism with atopic eczema. Allergy 2007, 62:766–772.

    Article  PubMed  CAS  Google Scholar 

  21. Howell MD: The role of human beta defensins and cathelicidins in atopic dermatitis. Curr Opin Allergy Clin Immunol 2007, 7:413–417.

    Article  PubMed  CAS  Google Scholar 

  22. Gläser R, Meyer-Hoffert U, Harder J, et al.: The antimicrobial protein psoriasin (S100A7) is upregulated in atopic dermatitis and after experimental skin barrier disruption. J Invest Dermatol 2009, 129:641–649.

    Article  PubMed  CAS  Google Scholar 

  23. Rieg S, Steffen H, Seeber S, et al.: Deficiency of dermcidinderived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. J Immunol 2005, 174:8003–8010.

    PubMed  CAS  Google Scholar 

  24. Hata TR, Kotol P, Jackson M, et al.: Administration of oral vitamin D induces cathelicidin production in atopic individuals. J Allergy Clin Immunol 2008, 122:829–831.

    Article  PubMed  CAS  Google Scholar 

  25. Yamasaki K, Schauber J, Coda A, et al.: Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. FASEB J 2006, 20:2068–2080.

    Article  PubMed  CAS  Google Scholar 

  26. Yamasaki K, Di NA, Bardan A, et al.: Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med 2007, 13:975–980.

    Article  PubMed  CAS  Google Scholar 

  27. Soruri A, Grigat J, Forssmann U, et al.: beta-Defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved. Eur J Immunol 2007, 37:2474–2486.

    Article  PubMed  CAS  Google Scholar 

  28. Grigat J, Soruri A, Forssmann U, et al.: Chemoattraction of macrophages, T lymphocytes, and mast cells is evolutionarily conserved within the human alpha-defensin family. J Immunol 2007, 179:3958–3965.

    PubMed  CAS  Google Scholar 

  29. Esnault S, Rosenthal LA, Wang DS, Malter JS: Thymic stromal lymphopoietin (TSLP) as a bridge between infection and atopy. Int J Clin Exp Pathol 2008, 1:325–330.

    PubMed  CAS  Google Scholar 

  30. Ebner S, Nguyen VA, Forstner M, et al.: Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen-presenting cells that induce proallergic T cells. J Allergy Clin Immunol 2007, 119:982–990.

    Article  PubMed  CAS  Google Scholar 

  31. Traidl-Hoffmann C, Mariani V, Hochrein H, et al.: Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper type 2 cell polarization. J Exp Med 2005, 201:627–636.

    Article  PubMed  CAS  Google Scholar 

  32. Jin H, Oyoshi MK, Le Y, et al.: IL-21R is essential for epicutaneous sensitization and allergic skin inflammation in humans and mice. J Clin Invest 2009, 119:47–60.

    PubMed  CAS  Google Scholar 

  33. Eyerich K, Pennino D, Scarponi C, et al.: IL-17 in atopic eczema: linking allergen-specific adaptive and microbial-triggered innate immune response. J Allergy Clin Immunol 2009, 123:59.e4–66.e4.

    Article  CAS  Google Scholar 

  34. He R, Oyoshi MK, Jin H, Geha RS: Epicutaneous antigen exposure induces a Th17 response that drives airway inflammation after inhalation challenge. Proc Natl Acad Sci U S A 2007, 104:15817–15822.

    Article  PubMed  CAS  Google Scholar 

  35. Sonkoly E, Muller A, Lauerma AI, et al.: IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol 2006, 117:411–417.

    Article  PubMed  CAS  Google Scholar 

  36. Neis MM, Peters B, Dreuw A, et al.: Enhanced expression levels of IL-31 correlate with IL-4 and IL-13 in atopic and allergic contact dermatitis. J Allergy Clin Immunol 2006, 118:930–937.

    Article  PubMed  CAS  Google Scholar 

  37. Schulz F, Marenholz I, Folster-Holst R, et al.: A common haplotype of the IL-31 gene influencing gene expression is associated with nonatopic eczema. J Allergy Clin Immunol 2007, 120:1097–1102.

    Article  PubMed  CAS  Google Scholar 

  38. Grimstad O, Sawanobori Y, Vestergaard C, et al.: Antiinterleukin-31-antibodies ameliorate scratching behaviour in NC/Nga mice: a model of atopic dermatitis. Exp Dermatol 2009, 18:35–43.

    Article  PubMed  CAS  Google Scholar 

  39. Illi S, von ME, Lau S, et al.: The natural course of atopic dermatitis from birth to age 7 years and the association with asthma. J Allergy Clin Immunol 2004, 113:925–931.

    Article  PubMed  Google Scholar 

  40. Bieber T: Atopic dermatitis. N Engl J Med 2008, 358:1483–1494.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology and Allergy, Rheinische Friedrich-Wilhelms-University Bonn, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany

    Thomas Bieber

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  1. Thomas Bieber
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  2. Natalija Novak
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Correspondence to Thomas Bieber.

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Bieber, T., Novak, N. Pathogenesis of atopic dermatitis: New developments. Curr Allergy Asthma Rep 9, 291–294 (2009). https://doi.org/10.1007/s11882-009-0041-2

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