Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases

Journal of Clinical Investigation

Volumn 122, Issue 2, 2012, Pages 440-447

  Kubo, Akiharu ^a   Nagao, Keisuke ^a   Amagai, Masayuki ^a  

^a KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

FILAGGRIN;

ATOPY; CELL MEMBRANE PERMEABILITY; DISEASE PREDISPOSITION; GENE MUTATION; GENETIC ASSOCIATION; HUMAN; LANGERHANS CELL; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SKIN FUNCTION; SKIN PERMEABILITY; SKIN SENSITIZATION; STRATUM CORNEUM; TIGHT JUNCTION;

ANIMALS; DERMATITIS, ATOPIC; EPIDERMIS; HUMANS; HYPERSENSITIVITY, IMMEDIATE; INTERMEDIATE FILAMENT PROTEINS; MUTATION; SKIN;

EID: 84856536446     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI57416     Document Type: Review

References (126)

1. Spergel JM. From atopic dermatitis to asthma: the atopic march. Ann Allergy Asthma Immunol. 2010;105(2):99-106.
2. Bieber T. Atopic dermatitis. N Engl J Med. 2008;358(14):1483-1494.
3. Furuse M, Tsukita S. Claudins in occluding junctions of humans and flies. Trends Cell Biol. 2006;16(4):181-188.
4. Cookson W. The immunogenetics of asthma and eczema: a new focus on the epithelium. Nat Rev Immunol. 2004;4(12):978-988. (Pubitemid 39620072)
5. Hackett T-L, Knight DA. The role of epithelial injury and repair in the origins of asthma. Curr Opin Allergy Clin Immunol. 2007;7(1):63-68. (Pubitemid 46095888)
6. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448(7152):427-434. (Pubitemid 47123518)
7. Hammad H, Lambrecht BN. Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma. Nat Rev Immunol. 2008;8(3):193-204. (Pubitemid 351323293)
8. McGrath JA, Uitto J. The filaggrin story: novel insights into skin-barrier function and disease. Trends Mol Med. 2008;14(1):20-27.
9. Schulzke JD, et al. Epithelial tight junctions in intestinal inflammation. Ann N Y Acad Sci. 2009;1165:294-300.
10. Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol. 2009;9(11):799-809.
11. Cork MJ, et al. Epidermal barrier dysfunction in atopic dermatitis. J Invest Dermatol. 2009;129(8):1892-1908.
12. Beck LA, Leung DY. Allergen sensitization through the skin induces systemic allergic responses. J Allergy Clin Immunol. 2000;106(5 suppl):S258-S263.
13. 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(13):2937-2946.
14. Aberg KM, et al. Co-regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers. J Invest Dermatol. 2008;128(4):917-925. (Pubitemid 351374295)
15. Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001;2(4):285-293. (Pubitemid 33676971)
16. Tsukita S, Yamazaki Y, Katsuno T, Tamura A. Tight junction-based epithelial microenvironment and cell proliferation. Oncogene. 2008;27(55):6930-6938.
17. Anderson JM, Van Itallie CM. Physiology and function of the tight junction. Cold Spring Harb Perspect Biol. 2009;1(2):a002584.
18. Farquhar MG, Palade GE. Cell junctions in amphibian skin. J Cell Biol. 1965;26(1):263-291.
19. Mittal AK, Whitear M. Keratinization of fish skin with special reference to the catfish Bagarius bagarius. Cell Tissue Res. 1979;202(2):213-230. (Pubitemid 10195446)
20. Hashimoto K. Intercellular spaces of the human epidermis as demonstrated with lanthanum. J Invest Dermatol. 1971;57(1):17-31.
21. Landmann L, Stolinski C, Martin B. The permeability barrier in the epidermis of the grass snake during the resting stage of the sloughing cycle. Cell Tissue Res. 1981;215(2):369-382. (Pubitemid 11149635)
22. 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(6):1099-1111. (Pubitemid 34839858)
23. Brandner JM, et al. Organization and formation of the tight junction system in human epidermis and cultured keratinocytes. Eur J Cell Biol. 2002;81(5):253-263. (Pubitemid 34568206)
24. Tsukita S, Furuse M. Claudin-based barrier in simple and stratified cellular sheets. Curr Opin Cell Biol. 2002;14(5):531-536. (Pubitemid 35251880)
25. Mackenzie IC. Relationship between mitosis and the ordered structure of the stratum corneum in mouse epidermis. Nature. 1970;226(5246):653-655.
26. Christophers E. Cellular architecture of the stratum corneum. J Invest Dermatol. 1971;56(3):165-169.
27. Mackenzie IC. Ordered structure of the epidermis. J Invest Dermatol. 1975;65(1):45-51.
28. Elias PM, et al. The secretory granular cell: the outermost granular cell as a specialized secretory cell. J Invest Dermatol Symp Proc. 1998;3(2):87-100. (Pubitemid 29135201)
29. Ishida-Yamamoto A, et al. Epidermal lamellar granules transport different cargoes as distinct aggregates. J Invest Dermatol. 2004;122(5):1137-1144. (Pubitemid 38651088)
30. Braff MH, Di Nardo A, Gallo RL. Keratinocytes store the antimicrobial peptide cathelicidin in lamellar bodies. J Invest Dermatol. 2005;124(2):394-400. (Pubitemid 40175887)
31. Oren A, Ganz T, Liu L, Meerloo T. In human epidermis, beta-defensin 2 is packaged in lamellar bodies. Exp Mol Pathol. 2003;74(2):180-182. (Pubitemid 36438667)
32. Kuroda S, et al. Perturbation of lamellar granule secretion by sodium caprate implicates epidermal tight junctions in lamellar granule function. J Dermatol Sci. 2010;59(2):107-114.
33. Montagna W, Parakkal P. The Structure And Function Of Skin. Orlando, Florida, USA: Academic Press; 1974.
34. Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol. 2005;6(4):328-340. (Pubitemid 40516899)
35. Simon M, et al. Refined characterization of corneodesmosin proteolysis during terminal differentiation of human epidermis and its relationship to desquamation. J Biol Chem. 2001;276(23):20292-20299.
36. Kaplan DH. In vivo function of Langerhans cells and dermal dendritic cells. Trends Immunol. 2010;31(12):446-451.
37. Merad M, Ginhoux F, Collin M. Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat Rev Immunol. 2008;8(12):935-947.
38. Nagao K, et al. Murine epidermal Langerhans cells and langerin-expressing dermal dendritic cells are unrelated and exhibit distinct functions. Proc Natl Acad Sci U S A. 2009;106(9):3312-3317.
39. Elentner A, et al. Langerhans cells are critical in the development of atopic dermatitis-like inflammation and symptoms in mice. J Cell Mol Med. 2009;13(8B):2658-2672.
40. Rescigno M, et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol. 2001;2(4):361-367. (Pubitemid 33706348)
41. Ichiyasu H, McCormack JM, McCarthy KM, Dombkowski D, Preffer FI, Schneeberger EE. Matrix metalloproteinase-9-deficient dendritic cells have impaired migration through tracheal epithelial tight junctions. Am J Respir Cell Mol Biol. 2004;30(6):761-770. (Pubitemid 38744524)
42. Niess JH, et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science. 2005;307(5707):254-258. (Pubitemid 40116240)
43. Takano K, et al. HLA-DR- and CD11c-positive dendritic cells penetrate beyond well-developed epithelial tight junctions in human nasal mucosa of allergic rhinitis. J Histochem Cytochem. 2005;53(5):611-619. (Pubitemid 40593974)
44. Chieppa M, Rescigno M, Huang AYC, Germain RN. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J Exp Med. 2006;203(13):2841-2852. (Pubitemid 46026162)
45. Blank F, Rothen-Rutishauser B, Gehr P. Dendritic cells and macrophages form a transepithelial network against foreign particulate antigens. Am J Respir Cell Mol Biol. 2007;36(6):669-677. (Pubitemid 46871421)
46. Ogasawara N, et al. Epithelial barrier and antigen uptake in lymphoepithelium of human adenoids. Acta Otolaryngol. 2011;131(2):116-123.
47. Wood LC, Jackson SM, Elias PM, Grunfeld C, Feingold KR. Cutaneous barrier perturbation stimulates cytokine production in the epidermis of mice. J Clin Invest. 1992;90(2):482-487.
48. Streilein JW, Lonsberry LW, Bergstresser PR. Depletion of epidermal langerhans cells and Ia immunogenicity from tape-stripped mouse skin. J Exp Med. 1982;155(3):863-871. (Pubitemid 12187859)
49. Lessard RJ, Wolff K, Winkelmann RK. The disappearance and regeneration of Langerhans cells following epidermal injury. J Invest Dermatol. 1968;50(2):171-179.
50. Nishijima T, Tokura Y, Imokawa G, Seo N, Furukawa F, Takigawa M. Altered permeability and disordered cutaneous immunoregulatory function in mice with acute barrier disruption. J Invest Dermatol. 1997;109(2):175-182. (Pubitemid 27337332)
51. Ouchi T, et al. Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome. J Exp Med. 2011;208(13):2607-2613.
52. Schröder JM, Harder J. Antimicrobial skin peptides and proteins. Cell Mol Life Sci. 2006;63(4):469-486.
53. Dai X, et al. Mite allergen is a danger signal for the skin via activation of inflammasome in keratinocytes. J Allergy Clin Immunol. 2011;127(3):806-814.
54. Nishibu A, Ward BR, Boes M, Takashima A. Roles for IL-1 and TNFalpha in dynamic behavioral responses of Langerhans cells to topical hapten application. J Dermatol Sci. 2007;45(1):23-30. (Pubitemid 44969511)
55. Briot A, et al. Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome. J Exp Med. 2009;206(5):1135-1147.
56. Ebner S, 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(4):982-990. (Pubitemid 46527821)
57. Pearton DJ, Dale BA, Presland RB. Functional analysis of the profilaggrin N-terminal peptide: identification of domains that regulate nuclear and cytoplasmic distribution. J Invest Dermatol. 2002;119(3):661-669.
58. Dale BA, Holbrook KA, Steinert PM. Assembly of stratum corneum basic protein and keratin filaments in macrofibrils. Nature. 1978;276(5689):729-731. (Pubitemid 9073536)
59. Scott IR, Harding CR. Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment. Dev Biol. 1986;115(1):84-92. (Pubitemid 16118872)
60. Rawlings AV, Matts PJ. Stratum corneum moisturization at the molecular level: an update in relation to the dry skin cycle. J Invest Dermatol. 2005;124(6):1099-1110. (Pubitemid 40847395)
61. Sandilands A, Sutherland C, Irvine AD, McLean WHI. Filaggrin in the frontline: role in skin barrier function and disease. J Cell Sci. 2009;122(9):1285-1294.
62. Smith FJD, et al. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet. 2006;38(3):337-342.
63. Palmer CN, 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(4):441-446.
64. Sandilands A, et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet. 2007;39(5):650-654. (Pubitemid 46676107)
65. O'Regan GM, Sandilands A, McLean WHI, Irvine AD. Filaggrin in atopic dermatitis. J Allergy Clin Immunol. 2008;122(4):689-693.
66. Akiyama M. FLG mutations in ichthyosis vulgaris and atopic eczema: spectrum of mutations and population genetics. Br J Dermatol. 2010;162(3):472-477.
67. Poninska J, et al. Filaggrin gene defects are independent risk factors for atopic asthma in a Polish population: a study in ECAP cohort. PLoS ONE. 2011;6(2):e16933.
68. Basu K, et al. Filaggrin null mutations are associated with increased asthma exacerbations in children and young adults. Allergy. 2008;63(9):1211- 1217.
69. Novak N, et al. Loss-of-function mutations in the filaggrin gene and allergic contact sensitization to nickel. J Invest Dermatol. 2008;128(6):1430-1435. (Pubitemid 351693185)
70. Rodríguez E, et al. Meta-analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease. J Allergy Clin Immunol. 2009;123(6):1361-1370.
71. Schuttelaar MLA, et al. Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and the interaction with cat exposure. Allergy. 2009;64(12):1758-1765.
72. Thyssen JP, et al. The association between null mutations in the filaggrin gene and contact sensitization to nickel and other chemicals in the general population. Br J Dermatol. 2010;162(6):1278-1285.
73. Brown SJ, 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.
74. Vercelli D. Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol. 2008;8(3):169-182. (Pubitemid 351323288)
75. Barnes KC. An update on the genetics of atopic dermatitis: scratching the surface in 2009. J Allergy Clin Immunol. 2010;125(1):16-29.
76. De Benedetto A, Qualia CM, Baroody FM, Beck LA. Filaggrin expression in oral, nasal, and esophageal mucosa. J Invest Dermatol. 2008;128(6):1594-1597. (Pubitemid 351693198)
77. Kodama M, et al. Strain-specific phenotypes of airway inflammation and bronchial hyperresponsiveness induced by epicutaneous allergen sensitization in BALB/c and C57BL/6 mice. Int Arch Allergy Immunol. 2010;152 suppl 1:67-74.
78. Spergel JM, Mizoguchi E, Brewer JP, Martin TR, Bhan AK, Geha RS. Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice. J Clin Invest. 1998;101(8):1614-1622. (Pubitemid 28198490)
79. Presland RB, Boggess D, Lewis SP, Hull C, Fleckman P, Sundberg JP. Loss of normal profilaggrin and filaggrin in flaky tail (ft/ft) mice: an animal model for the filaggrin-deficient skin disease ichthyosis vulgaris. J Invest Dermatol. 2000;115(6):1072-1081. (Pubitemid 32037453)
80. Sundberg JP. The flaky tail (ft) mutation. In: Sundberg JP, ed. Handbook of Mouse Mutations with Skin and Hair Abnormalities. Animal Models and Biochemical Tools. Vol. 2. Ann Arbor, Michigan, USA: CRC Press; 1984:269-273.
81. Fallon PG, et al. A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet. 2009;41(5):602-608.
82. Scharschmidt TC, et al. Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens. J Allergy Clin Immunol. 2009;124(3):496-506.
83. Moniaga CS, et al. Flaky tail mouse denotes human atopic dermatitis in the steady state and by topical application with Dermatophagoides pteronyssinus extract. Am J Pathol. 2010;176(5):2385-2393.
84. Deraison C, 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. (Pubitemid 47378698)
85. Ovaere P, Lippens S, Vandenabeele P, Declercq W. The emerging roles of serine protease cascades in the epidermis. Trends Biochem Sci. 2009;34(9):453-463.
86. Walley AJ, et al. Gene polymorphism in Netherton and common atopic disease. Nat Genet. 2001;29(2):175-178. (Pubitemid 32952654)
87. Kato A, Fukai K, Oiso N, Hosomi N, Murakami T, Ishii M. Association of SPINK5 gene polymorphisms with atopic dermatitis in the Japanese population. Br J Dermatol. 2003;148(4):665-669. (Pubitemid 36629743)
88. Nishio Y, et al. Association between polymorphisms in the SPINK5 gene and atopic dermatitis in the Japanese. Genes Immun. 2003;4(7):515-517. (Pubitemid 38967619)
89. Chavanas S, et al. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet. 2000;25(2):141-142. (Pubitemid 30394980)
90. Frenk E, Mevorah B. Ichthyosis linearis circumflexa Comèl with Trichorrhexis invaginata (Netherton's Syndrom): an ultrastructural study of the skin changes. Arch Dermatol Forsch. 1972;245(1):42-49.
91. Fartasch M, Williams ML, Elias PM. Altered lamellar body secretion and stratum corneum membrane structure in Netherton syndrome: differentiation from other infantile erythrodermas and pathogenic implications. Arch Dermatol. 1999;135(7):823-832. (Pubitemid 29330807)
92. Müller FB, et al. Genetic analysis of a severe case of Netherton syndrome and application for prenatal testing. Br J Dermatol. 2002;146(3):495-499. (Pubitemid 34603824)
93. Yang T, Liang D, Koch PJ, Hohl D, Kheradmand F, Overbeek PA. Epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin in Spink5-/- mice. Genes Dev. 2004;18(19):2354-2358. (Pubitemid 39304682)
94. Descargues P, et al. Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity. Nat Genet. 2005;37(1):56-65. (Pubitemid 40070940)
95. Descargues P, et al. Corneodesmosomal cadherins are preferential targets of stratum corneum trypsinand chymotrypsin-like hyperactivity in Netherton syndrome. J Invest Dermatol. 2006;126(7):1622-1632.
96. Vasilopoulos Y, 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(1):62-66. (Pubitemid 38833464)
97. Oji V, 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.
98. Bonnart C, et al. Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing. J Clin Invest. 2010;120(3):871-882.
99. Matsui T, et al. Skin-specific aspartic protease SASPase regulate stratum corneum hydration through profilaggrin processing. EMBO Mol Med. 2011;3(6):320-333.
100. Denecker G, et al. Caspase-14 protects against epidermal UVB photodamage and water loss. Nat Cell Biol. 2007;9(6):666-674. (Pubitemid 47214729)
101. Hoste E, et al. Caspase-14 is required for filaggrin degradation to natural moisturizing factors in the skin [published online ahead of print June 9, 2011]. J Invest Dermatol. doi:10.1038/jid.2011.153.
102. Kamata Y, et al. Neutral cysteine protease bleomycin hydrolase is essential for the breakdown of deiminated filaggrin into amino acids. J Biol Chem. 2009;284(19):12829-12836.
103. Kamata Y, et al. Bleomycin hydrolase is regulated biphasically in a differentiation- and cytokine-dependent manner: relevance to atopic dermatitis. J Biol Chem. 2011;286(10):8204-8212.
104. Schwartz DR, Homanics GE, Hoyt DG, Klein E, Abernethy J, Lazo JS. The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance. Proc Natl Acad Sci U S A. 1999;96(8):4680-4685. (Pubitemid 29190396)
105. Morita K, et al. Molecular architecture of tight junctions of periderm differs from that of the maculae occludentes of epidermis. J Invest Dermatol. 2002;118(6):1073-1079. (Pubitemid 34639188)
106. Turksen K, Troy T-C. Permeability barrier dysfunction in transgenic mice overexpressing claudin 6. Development. 2002;129(7):1775-1784. (Pubitemid 34874193)
107. Hadj-Rabia S, et al. Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. Gastroenterology. 2004;127(5):1386-1390. (Pubitemid 39457765)
108. Feldmeyer L, Huber M, Fellmann F, Beckmann JS, Frenk E, Hohl D. Confirmation of the origin of NISCH syndrome. Hum Mutat. 2006;27(5):408-410. (Pubitemid 43673326)
109. De Benedetto A, et al. Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol. 2011;127(3):773-786.
110. Uitto J, McGrath JA, Rodeck U, Bruckner-Tuderman L, Robinson EC. Progress in epidermolysis bullosa research: toward treatment and cure. J Invest Dermatol. 2010;130(7):1778-1784.
111. Wan H, et al. Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions. J Clin Invest. 1999;104(1):123-133. (Pubitemid 29534352)
112. Hammad H, Chieppa M, Perros F, Willart MA, Germain RN, Lambrecht BN. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med. 2009;15(4):410-416.
113. Kato T, et al. Mite serine protease activates protease-activated receptor-2 and induces cytokine release in human keratinocytes. Allergy. 2009;64(9):1366-1374.
114. Vu AT, et al. Staphylococcus aureus membrane and diacylated lipopeptide induce thymic stromal lymphopoietin in keratinocytes through the Toll-like receptor 2-Toll-like receptor 6 pathway. J Allergy Clin Immunol. 2010;126(5):985-993.
115. Kim BE, et al. TNF-alpha downregulates filaggrin and loricrin through c-Jun N-terminal kinase: role for TNF-alpha antagonists to improve skin barrier. J Invest Dermatol. 2011;131(6):1272-1279.
116. Howell MD, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2007;120(1):150-155. (Pubitemid 46990506)
117. Gutowska-Owsiak D, Schaupp AL, Salimi M, Taylor S, Ogg GS. Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes. Br J Dermatol. 2011;165(3):492-498.
118. Hvid M, Vestergaard C, Kemp K, Christensen GB, Deleuran B, Deleuran M. IL-25 in atopic dermatitis: a possible link between inflammation and skin barrier dysfunction? J Invest Dermatol. 2011;131(1):150-157.
119. Hvid M, Johansen C, Deleuran B, Kemp K, Deleuran M, Vestergaard C. Regulation of caspase 14 expression in keratinocytes by inflammatory cytokines - a possible link between reduced skin barrier function and inflammation? Exp Dermatol. 2011;20(8):633-636.
120. Ozcan E, Notarangelo LD, Geha RS. Primary immune deficiencies with aberrant IgE production. J Allergy Clin Immunol. 2008;122(6):1054-1062.
121. Lesiak A, et al. Combined occurrence of filaggrin mutations and IL-10 or IL-13 polymorphisms predisposes to atopic dermatitis. Exp Dermatol. 2011;20(6):491-495.
122. Simpson EL, Berry TM, Brown PA, Hanifin JM. A pilot study of emollient therapy for the primary prevention of atopic dermatitis. J Am Acad Dermatol. 2010;63(4):587-593.
123. Stefansson K, et al. Activation of proteinase-activated receptor-2 by human kallikrein-related peptidases. J Invest Dermatol. 2008;128(1):18-25. (Pubitemid 350249381)
124. Enk AH, Angeloni VL, Udey MC, Katz SI. An essential role for Langerhans cell-derived IL-1 beta in the initiation of primary immune responses in skin. J Immunol. 1993;150(9):3698-3704. (Pubitemid 23129751)
125. Vasilopoulos Y, et al. A nonsynonymous substitution of cystatin A, a cysteine protease inhibitor of house dust mite protease, leads to decreased mRNA stability and shows a significant association with atopic dermatitis. Allergy. 2007;62(5):514-519. (Pubitemid 46608369)
126. Hubiche T, et al. Analysis of SPINK 5, KLK 7 and FLG genotypes in a French atopic dermatitis cohort. Acta Dermato-Venereologica. 2007;87(6):499-505. (Pubitemid 351373393)