Murine Models of Atopic Dermatitis

  • T. Brzoska
  • T. A. Luger
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 50)

7.7 Conclusions

In accordance with the complex immunopathological findings in AD, many different murine models have been established, each focusing on different aspects of the disease. Thus several transgenic and knockout mouse models were helpful to a certain degree in improving our understanding of AD pathophysiology. However, genetic manipulation of a single cytokine obviously cannot mirror the whole picture of a complex disease such as AD. Neither the interaction between selected cytokines nor the entire pathological pathways can be completely evaluated with these models. Yet this type of mouse model has great potential for increasing our knowledge of AD pathology and for investigating the mechanisms of drug activities. Mice with spontaneous mutations resulting in an AD phenotype allow investigations on a broader scale, as do animals treated with antigens in order to induce AD. Combinations of the different approaches increase the size and versatility of the toolkit available, as shown by deletion of genes in NC/Nga mice, thus allowing even deeper insights in the mechanism of AD. Mice with a spontaneous AD phenotype are also suitable for drug testing and development. This also applies to the chimeric SCID-hu mouse, which allows assessment of the interaction between human skin and selected human cell populations. However, models should be chosen carefully and manipulations should be done only after appropriate consideration of side effects or unwanted additional effects.


Mast Cell Atopic Dermatitis Allergy Clin Immunol Allergic Dermatitis Lergy Clin Immunol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aioi A, Tonogaito H, Suto H, Hamada K, Ra CR, Ogawa H, Maibach H, and Matsuda H (2001) Impairment of skin barrier function in NC/Nga Tnd mice as a possible model for atopic dermatitis. Br J Dermatol 144:12–18PubMedCrossRefGoogle Scholar
  2. Akdis CA and Akdis M (2003) Immunological differences between intrinsic and extrinsic types of atopic dermatitis. Clin Exp Allergy 33:1618–1621PubMedCrossRefGoogle Scholar
  3. Alenius H, Laouini D, Woodward A, Mizoguchi E, Bhan AK, Castigli E, Oettgen HC, and Geha RS (2002) Mast cells regulate IFNγ expression in the skin and circulating IgE levels in allergen-induced skin inflammation. J Allergy Clin Immunol 109:106–113PubMedCrossRefGoogle Scholar
  4. Ansel JC, Kaynard AH, Armstrong CA, Olerud J, Bunnett N, and Payan D (1996) Skin-nervous system interactions. J Invest Dermatol 106:198–204PubMedCrossRefGoogle Scholar
  5. Biedermann T, Schwarzler C, Lametschwandtner G, Thoma G, Carballido-Perrig N, Kund J, de Vries JE, Rot A, and Carballido JM (2002) Targeting CLA/E-selectin interactions prevents CCR4-mediated recruitment of human Th2 memory cells to human skin in vivo. Eur J Immunol 32:3171–3180PubMedCrossRefGoogle Scholar
  6. Bosma GC, Custer RP, Bosma MJ (1983) A severe combined immunodeficiency mutation in the mouse. Nature 301:527–530PubMedCrossRefGoogle Scholar
  7. Bossie A, Vitetta ES (1991) IFNγ enhances secretion of IgG2a from IgG2a-committed LPS-stimulated murine B cells: implications for the role of IFNγ in class switching. Cell Immunol 135:95–104PubMedCrossRefGoogle Scholar
  8. Boyce JA (2003) Mast cells: beyond IgE. J Allergy Clin Immunol 111:24–32PubMedCrossRefGoogle Scholar
  9. Breuer K, Wittmann M, Bosche B, Kapp A, and Werfel T (2000) Severe atopic dermatitis is associated with sensitization to staphylococcal enterotoxin B (SEB). Allergy 55:551–555PubMedCrossRefGoogle Scholar
  10. Brown MA and Hural J (1997) Functions of IL-4 and control of its expression. Crit Rev Immunol 17:1–32PubMedGoogle Scholar
  11. Bunikowski R, Mielke ME, Skarabis H, Worm M, Anagnostopoulos I, Kolde G, Wahn U, and Renz H (2000) Evidence for a disease-promoting effect of Staphylococcus aureus-derived exotoxins in atopic dermatitis. J Allergy Clin Immunol 105:814–819PubMedCrossRefGoogle Scholar
  12. Carballido JM, Biedermann T, Schwarzler C, and de Vries JE (2003) The SCID-hu Skin mouse as a model to investigate selective chemokine mediated homing of human T-lymphocytes to the skin in vivo. J Immunol Methods 273:125–135PubMedCrossRefGoogle Scholar
  13. Chan LS, Robinson N, and Xu L (2001) Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis. J Invest Dermatol 117:977–983PubMedCrossRefGoogle Scholar
  14. Cho SH, Strickland I, Tomkinson A, Fehringer AP, Gelfand EW, and Leung DY (2001) Preferential binding of Staphylococcus aureus to skin sites of Th2-mediated inflammation in a murine model. J Invest Dermatol 116:658–663PubMedCrossRefGoogle Scholar
  15. Chomarat P and Banchereau J (1997) An update on interleukin-4 and its receptor. Eur Cytokine Netw 8:333–344PubMedGoogle Scholar
  16. Chomarat P and Banchereau J (1998) Interleukin-4 and interleukin-13: their similarities and discrepancies. Int Rev Immunol 17:1–52PubMedGoogle Scholar
  17. Costa JJ, Demetri GD, Harrist TJ, Dvorak AM, Hayes DF, Merica EA, Menchaca DM, Gringeri AJ, Schwartz LB, and Galli SJ (1996) Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo. J Exp Med 183:2681–2686PubMedCrossRefGoogle Scholar
  18. Dinarello CA and Fantuzzi G (2003) Interleukin-18 and host defense against infection. J Infect Dis 187[Suppl 2]:S370–S384PubMedCrossRefGoogle Scholar
  19. Eigenmann PA, Sicherer SH, Borkowski TA, Cohen BA, and Sampson HA (1998) Prevalence of IgE-mediated food allergy among children with atopic dermatitis. Pediatrics 101:E8PubMedCrossRefGoogle Scholar
  20. Elbe-Burger A, Egyed A, Olt S, Klubal R, Mann U, Rappersberger K, Rot A, and Stingl G (2002) Overexpression of IL-4 alters the homeostasis in the skin. J Invest Dermatol 118:767–778PubMedCrossRefGoogle Scholar
  21. Gaide O, Favier B, Legler DF, Bonnet D, Brissoni B, Valitutti S, Bron C, Tschopp J, and Thome M (2002) CARMA1 is a critical lipid graft-associated regulator of TCR-induced NF-κB activation. Nat Immunol 3:836–843PubMedCrossRefGoogle Scholar
  22. Galli SJ, Wedemeyer J, and Tsai M (2002) Analyzing the roles of mast cells and basophils in host defense and other biological responses. Int J Hematol 75:363–369PubMedCrossRefGoogle Scholar
  23. Gluckman JC, Canque B, Chapuis F, and Rosenzwajg M (1997) In vitro generation of human dendritic cells and cell therapy. Cytokines Cell Mol Ther 3:187–196PubMedGoogle Scholar
  24. Graham MB, Dalton DK, Giltinan D, Braciale VL, Stewart TA, and Braciale TJ (1993) Response to influenza infection in mice with a targeted disruption in the interferon γ gene. J Exp Med 178:1725–1732PubMedCrossRefGoogle Scholar
  25. Grewal IS and Flavell RA (1996) The role of CD40 ligand in costimulation and T-cell activation. Immunol Rev 153:85–106PubMedCrossRefGoogle Scholar
  26. Grewe M, Czech W, Morita A, Werfel T, Klammer M, Kapp A, Ruzicka T, Schopf E, and Krutmann J (1998) Human eosinophils produce biologically active IL-12: implications for control of T cell responses. J Immunol 161:415–420PubMedGoogle Scholar
  27. Habu Y, Seki S, Takayama E, Ohkawa T, Koike Y, Ami K, Majima T, and Hiraide H (2001) The mechanism of a defective IFNγ response to bacterial toxins in an atopic dermatitis model, NC/Nga mice, and the therapeutic effect of IFNγ, IL-12, or IL-18 on dermatitis. J Immunol 166:5439–5447PubMedGoogle Scholar
  28. Hagermark O, Rajka G, and Bergvist U (1972) Experimental itch in human skin elicited by rat mast cell chymase. Acta Derm Venereol 52:125–128Google Scholar
  29. Hanissian SH and Geha RS (1997) Jak3 is associated with CD40 and is critical for CD40 induction of gene expression in B cells. Immunity 6:379–387PubMedCrossRefGoogle Scholar
  30. Hara H, Wada T, Bakal C, Kozieradzki I, Suzuki S, Suzuki N, Nghiem M, Griffiths EK, Krawczyk C, Bauer B, D’Acquisto F, Ghosh S, Yeh WC, Baier G, Rottapel R, and Penninger JM (2003) The MAGUK family protein CARD11 is essential for lymphocyte activation. Immunity 18:763–775PubMedCrossRefGoogle Scholar
  31. Hashimoto S, Suzuki T, Dong HY, Nagai S, Yamazaki N, and Matsushima K (1999) Serial analysis of gene expression in human monocyte-derived dendritic cells. Blood 94:845–852PubMedGoogle Scholar
  32. He S and Walls AF (1998a) Human mast cell chymase induces the accumulation of neutrophils, eosinophils and other inflammatory cells in vivo. Br J Pharmacol 125:1491–1500PubMedCrossRefGoogle Scholar
  33. He S and Walls AF (1998b) The induction of a prolonged increase in microvascular permeability by human mast cell chymase. Eur J Pharmacol 352:91–98PubMedCrossRefGoogle Scholar
  34. Heath H, Qin S, Rao P, Wu L, LaRosa G, Kassam N, Ponath PD, and Mackay CR (1997) Chemokine receptor usage by human eosinophils. The importance of CCR3 demonstrated using an antagonistic monoclonal antibody. J Clin Invest 99:178–184PubMedCrossRefGoogle Scholar
  35. Hershey GK, Friedrich MF, Esswein LA, Thomas ML, and Chatila TA (1997) The association of atopy with a gain-of-function mutation in the α subunit of the interleukin-4 receptor. N Engl J Med 337:1720–1725PubMedCrossRefGoogle Scholar
  36. Hidalgo LG and Halloran PF (2002) Role of IFNγ in allograft rejection. Crit Rev Immunol 22:317–349PubMedGoogle Scholar
  37. Ihle JN and Kerr IM (1995) Jaks and Stats in signaling by the cytokine receptor superfamily. Trends Genet 11:69–74PubMedCrossRefGoogle Scholar
  38. Imai T, Baba M, Nishimura M, Kakizaki M, Takagi S, and Yoshie O (1997) The T cell-directed CC chemokine TARC is a highly specific biological ligand for CC chemokine receptor 4. J Biol Chem 272:15036–15042PubMedCrossRefGoogle Scholar
  39. Imai T, Nagira M, Takagi S, Kakizaki M, Nishimura M, Wang J, Gray PW, Matsushima K, and Yoshie O (1999) Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. Int Immunol 11:81–88PubMedCrossRefGoogle Scholar
  40. Jeong CW, Ahn KS, Rho NK, Park YD, Lee DY, Lee JH, Lee ES, and Yang JM (2003) Differential in vivo cytokine mRNA expression in lesional skin of intrinsic vs. extrinsic atopic dermatitis patients using semiquantitative RT-PCR. Clin Exp Allergy 33:1717–1724PubMedCrossRefGoogle Scholar
  41. Johansson SG, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela T, Kowalski ML, Mygind N, Ring J, van Cauwenberge P, Hage-Hamsten M, and Wuthrich B (2001) A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy 56:813–824PubMedCrossRefGoogle Scholar
  42. Jun JE and Goodnow CC (2003) Scaffolding of antigen receptors for immunogenic versus tolerogenic signaling. Nat Immunol 4:1057–1064PubMedCrossRefGoogle Scholar
  43. Jun JE, Wilson LE, Vinuesa CG, Lesage S, Blery M, Miosge LA, Cook MC, Kucharska EM, Hara H, Penninger JM, Domashenz H, Hong NA, Glynne RJ, Nelms KA, and Goodnow CC (2003) Identifying the MAGUK protein Carma-1 as a central regulator of humoral immune responses and atopy by genome-wide mouse mutagenesis. Immunity 18: 751–762PubMedCrossRefGoogle Scholar
  44. Kaplan AP (2001) Chemokines, chemokine receptors and allergy. Int Arch Allergy Immunol 124:423–431PubMedCrossRefGoogle Scholar
  45. Kaplan MH, Schindler U, Smiley ST, and Grusby MJ (1996) Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity 4:313–319PubMedCrossRefGoogle Scholar
  46. Kieffer M, Bergbrant IM, Faergemann J, Jemec GB, Ottevanger V, Stahl SP, and Svejgaard E (1990) Immune reactions to Pityrosporum ovale in adult patients with atopic and seborrheic dermatitis. J Am Acad Dermatol 22: 739–742PubMedCrossRefGoogle Scholar
  47. Kinaciyan T, Natter S, Kraft D, Stingl G, and Valenta R (2002) IgE autoantibodies monitored in a patient with atopic dermatitis under cyclosporin A treatment reflect tissue damage. J Allergy Clin Immunol 109:717–719PubMedCrossRefGoogle Scholar
  48. Kirchgessner CU, Patil CK, Evans JW, Cuomo CA, Fried LM, Carter T, Oettinger MA, and Brown JM (1995) DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science 267:1178–1183PubMedCrossRefGoogle Scholar
  49. Krishnaswamy G, Kelley J, Johnson D, Youngberg G, Stone W, Huang SK, Bieber J, and Chi DS (2001) The human mast cell: functions in physiology and disease. Front Biosci 6:D1109–D1127PubMedCrossRefGoogle Scholar
  50. Kung TT, Stelts D, Zurcher JA, Jones H, Umland SP, Kreutner W, Egan RW, and Chapman RW (1995) Mast cells modulate allergic pulmonary eosinophilia in mice. Am J Respir Cell Mol Biol 12:404–409PubMedGoogle Scholar
  51. Laman JD, Claassen E, and Noelle RJ (1996) Functions of CD40 and its ligand, gp39 (CD40L). Crit Rev Immunol 16:59–108PubMedGoogle Scholar
  52. Laouini D, Alenius H, Bryce P, Oettgen H, Tsitsikov E, and Geha RS (2003) IL-10 is critical for Th2 responses in a murine model of allergic dermatitis. J Clin Invest 112:1058–1066PubMedGoogle Scholar
  53. Leung DY (2000) Atopic dermatitis: new insights and opportunities for therapeutic intervention. J Allergy Clin Immunol 105:860–876PubMedCrossRefGoogle Scholar
  54. Leung DY, Harbeck R, Bina P, Reiser RF, Yang E, Norris DA, Hanifin JM, and Sampson HA (1993) Presence of IgE antibodies to staphylococcal exotoxins on the skin of patients with atopic dermatitis. Evidence for a new group of allergens. J Clin Invest 92:1374–1380PubMedCrossRefGoogle Scholar
  55. Leung DY, Hauk P, Strickland I, Travers JB, and Norris DA (1998) The role of superantigens in human diseases: therapeutic implications for the treatment of skin diseases. Br J Dermatol 139[Suppl 53]: 17–29PubMedCrossRefGoogle Scholar
  56. Lever R, MacDonald C, Waugh P, and Aitchison T (1998) Randomised controlled trial of advice on an egg exclusion diet in young children with atopic eczema and sensitivity to eggs. Pediatr Allergy Immunol 9:13–19PubMedCrossRefGoogle Scholar
  57. Leyden JJ, Marples RR, and Kligman AM (1974) Staphylococcus aureus in the lesions of atopic dermatitis. Br J Dermatol 90:525–530PubMedCrossRefGoogle Scholar
  58. Li XM, Kleiner G, Huang CK, Lee SY, Schofield B, Soter NA, and Sampson HA (2001) Murine model of atopic dermatitis associated with food hypersensitivity. J Allergy Clin Immunol 107:693–702PubMedCrossRefGoogle Scholar
  59. Longley BJ, Tyrrell L, Ma Y, Williams DA, Halaban R, Langley K, Lu HS, and Schechter NM (1997) Chymase cleavage of stem cell factor yields a bioactive, soluble product. Proc Natl Acad Sci USA 94:9017–9021PubMedCrossRefGoogle Scholar
  60. Ma W, Bryce PJ, Humbles AA, Laouini D, Yalcindag A, Alenius H, Friend DS, Oettgen HC, Gerard C, and Geha RS (2002) CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. J Clin Invest 109:621–628PubMedGoogle Scholar
  61. Magram J, Connaughton SE, Warrier RR, Carvajal DM, Wu CY, Ferrante J, Stewart C, Sarmiento U, Faherty DA, and Gately MK (1996) IL-12-deficient mice are defective in IFNγ production and type 1 cytokine responses. Immunity 4:471–481PubMedCrossRefGoogle Scholar
  62. Martin R (2003) Interleukin 4 treatment of psoriasis: are pleiotropic cytokines suitable therapies for autoimmune diseases? Trends Pharmacol Sci 24:613–616PubMedCrossRefGoogle Scholar
  63. Matsuda H, Watanabe N, Geba GP, Sperl J, Tsudzuki M, Hiroi J, Matsumoto M, Ushio H, Saito S, Askenase PW, and Ra C (1997) Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice. Int Immunol 9:461–466PubMedCrossRefGoogle Scholar
  64. Matsumoto M, Ra C, Kawamoto K, Sato H, Itakura A, Sawada J, Ushio H, Suto H, Mitsuishi K, Hikasa Y, and Matsuda H (1999) IgE hyperproduction through enhanced tyrosine phosphorylation of Janus kinase 3 in NC/ Nga mice, a model for human atopic dermatitis. J Immunol 162:1056–1063PubMedGoogle Scholar
  65. Matsuoka H, Maki N, Yoshida S, Arai M, Wang J, Oikawa Y, Ikeda T, Hirota N, Nakagawa H, and Ishii A (2003) A mouse model of the atopic eczema/dermatitis syndrome by repeated application of a crude extract of house-dust mite Dermatophagoides farinae. Allergy 58:139–145PubMedCrossRefGoogle Scholar
  66. Mehling A, Loser K, Varga G, Metze D, Luger TA, Schwarz T, Grabbe S, and Beissert S (2001) Overexpression of CD40 ligand in murine epidermis results in chronic skin inflammation and systemic autoimmunity. J Exp Med 194:615–628PubMedCrossRefGoogle Scholar
  67. Mihm MC, Jr., Soter NA, Dvorak HF, and Austen KF (1976) The structure of normal skin and the morphology of atopic eczema. J Invest Dermatol 67:305–312PubMedCrossRefGoogle Scholar
  68. Moore KW, de Waal MR, Coffman RL, and O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765PubMedCrossRefGoogle Scholar
  69. Moore KW, O’Garra A, de Waal MR, Vieira P, and Mosmann TR (1993) Interleukin-10. Annu Rev Immunol 11:165–190PubMedCrossRefGoogle Scholar
  70. Nagai H, Yamaguchi S, Maeda Y, and Tanaka H (1996) Role of mast cells, eosinophils and IL-5 in the development of airway hyperresponsiveness in sensitized mice. Clin Exp Allergy 26:642–647PubMedCrossRefGoogle Scholar
  71. Natori K, Tamari M, Watanabe O, Onouchi Y, Shiomoto Y, Kubo S, and Nakamura Y (1999) Mapping of a gene responsible for dermatitis in NOA (Naruto Research Institute Otsuka Atrichia) mice, an animal model of allergic dermatitis. J Hum Genet 44:372–376PubMedCrossRefGoogle Scholar
  72. Nomura I, Gao B, Boguniewicz M, Darst MA, Travers JB, and Leung DY (2003 a) Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analysis. J Allergy Clin Immunol 112:1195–1202PubMedCrossRefGoogle Scholar
  73. Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, Darst MA, Gao B, Boguniewicz M, Travers JB, and Leung DY (2003b) Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol 171:3262–3269PubMedGoogle Scholar
  74. Ochi H, Hirani WM, Yuan Q, Friend DS, Austen KF, and Boyce JA (1999) T helper cell type 2 cytokine-mediated comitogenic responses and CCR3 expression during differentiation of human mast cells in vitro. J Exp Med 190:267–280PubMedCrossRefGoogle Scholar
  75. Piloto VL, Gomez Echevarria AH, Valdes Sanchez AF, Ochoa OC, Chong LA, and Mier NG (1990) Atopic dermatitis. Findings of skin biopsies. Allergol Immunopathol (Madr) 18:321–324Google Scholar
  76. Pomerantz JL, Denny EM, and Baltimore D (2002) CARD11 mediates factor-specific activation of NF-κB by the T cell receptor complex. EMBO J 21:5184–5194PubMedCrossRefGoogle Scholar
  77. Quelle FW, Shimoda K, Thierfelder W, Fischer C, Kim A, Ruben SM, Cleveland JL, Pierce JH, Keegan AD, and Nelms K (1995) Cloning of murine Stat6 and human Stat6, Stat proteins that are tyrosine phosphorylated in responses to IL-4 and IL-3 but are not required for mitogenesis. Mol Cell Biol 15:3336–3343PubMedGoogle Scholar
  78. Remitz A, Kyllonen H, Granlund H, and Reitamo S (2001) Tacrolimus ointment reduces staphylococcal colonization of atopic dermatitis lesions. J Allergy Clin Immunol 107:196–197PubMedCrossRefGoogle Scholar
  79. Ruzicka T (1998) Atopic eczema between rationality and irrationality. Arch Dermatol 134:1462–1469PubMedCrossRefGoogle Scholar
  80. Sallusto F, Mackay CR, and Lanzavecchia A (1997) Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science 277: 2005–2007PubMedCrossRefGoogle Scholar
  81. Sallusto F, Palermo B, Lenig D, Miettinen M, Matikainen S, Julkunen I, Forster R, Burgstahler R, Lipp M, and Lanzavecchia A (1999) Distinct patterns and kinetics of chemokine production regulate dendritic cell function. Eur J Immunol 29:1617–1625PubMedCrossRefGoogle Scholar
  82. Sampson HA (1999) Food allergy. Part 1: immunopathogenesis and clinical disorders. J Allergy Clin Immunol 103:717–728PubMedCrossRefGoogle Scholar
  83. Sampson HA (2001) Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol 107:891–896PubMedCrossRefGoogle Scholar
  84. Sasakawa T, Higashi Y, Sakuma S, Hirayama Y, Sasakawa Y, Ohkubo Y, Goto T, Matsumoto M, and Matsuda H (2001) Atopic dermatitis-like skin lesions induced by topical application of mite antigens in NC/Nga mice. Int Arch Allergy Immunol 126:239–247PubMedCrossRefGoogle Scholar
  85. Scalabrin DM, Bavbek S, Perzanowski MS, Wilson BB, Platts-Mills TA, and Wheatley LM (1999) Use of specific IgE in assessing the relevance of fungal and dust mite allergens to atopic dermatitis: a comparison with asthmatic and nonasthmatic control subjects. J Allergy Clin Immunol 104:1273–1279PubMedCrossRefGoogle Scholar
  86. Schon MP, Zollner TM, and Boehncke WH (2003) The molecular basis of lymphocyte recruitment to the skin: clues for pathogenesis and selective therapies of inflammatory disorders. J Invest Dermatol 121:951–962PubMedCrossRefGoogle Scholar
  87. Schroder K, Hertzog PJ, Ravasi T, and Hume DA (2004) Interferon-γ: an overview of signals, mechanisms and functions. J Leukoc Biol 75:163–189PubMedCrossRefGoogle Scholar
  88. Schultz LF, Diepgen T, and Svensson A (1996) The occurrence of atopic dermatitis in north Europe: an international questionnaire study. J Am Acad Dermatol 34:760–764CrossRefGoogle Scholar
  89. Shimoda K, van Deursen J, Sangster MY, Sarawar SR, Carson RT, Tripp RA, Chu C, Quelle FW, Nosaka T, Vignali DA, Doherty PC, Grosveld G, Paul WE, and Ihle JN (1996) Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene. Nature 380:630–633PubMedCrossRefGoogle Scholar
  90. Spergel JM, Mizoguchi E, Brewer JP, Martin TR, Bhan AK, and Geha RS (1998) Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice. J Clin Invest 101:1614–1622PubMedCrossRefGoogle Scholar
  91. Spergel JM, Mizoguchi E, Oettgen H, Bhan AK, and Geha RS (1999) Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. J Clin Invest 103:1103–1111PubMedCrossRefGoogle Scholar
  92. Stoll S, Jonuleit H, Schmitt E, Muller G, Yamauchi H, Kurimoto M, Knop J, and Enk AH (1998) Production of functional IL-18 by different subtypes of murine and human dendritic cells (DC): DC-derived IL-18 enhances IL-12-dependent Thl development. Eur J Immunol 28:3231–3239PubMedCrossRefGoogle Scholar
  93. Suto H, Matsuda H, Mitsuishi K, Hira K, Uchida T, Unno T, Ogawa H, and Ra C (1999) NC/Nga mice: a mouse model for atopic dermatitis. Int Arch Allergy Immunol 120[Suppll]:70–75PubMedCrossRefGoogle Scholar
  94. Takeda K, Tanaka T, Shi W, Matsumoto M, Minami M, Kashiwamura S, Nakanishi K, Yoshida N, Kishimoto T, and Akira S (1996) Essential role of Stat6 in IL-4 signalling. Nature 380:627–630PubMedCrossRefGoogle Scholar
  95. Tan BB, Weald D, Strickland I, and Friedmann PS (1996) Double-blind controlled trial of effect of housedust-mite allergen avoidance on atopic dermatitis. Lancet 347:15–18PubMedCrossRefGoogle Scholar
  96. Tepper RI, Levinson DA, Stanger BZ, Campos-Torres J, Abbas AK, and Leder P (1990) IL-4 induces allergic-like inflammatory disease and alters T cell development in transgenic mice. Cell 62:457–467PubMedCrossRefGoogle Scholar
  97. Tortolani PJ, Lai BK, Riva A, Johnston JA, Chen YQ, Reaman GH, Beck-with M, Longo D, Ortaldo JR, and Bhatia K (1995) Regulation of JAK3 expression and activation in human B cells and B cell malignancies. J Immunol 155:5220–5226PubMedGoogle Scholar
  98. Tsudzuki M, Watanabe N, Wada A, Nakane Y, Hiroi J, and Matsuda H (1997) Genetic analyses for dermatitis and IgE hyperproduction in the NC/Nga mouse. Immunogenetics 47:88–90PubMedCrossRefGoogle Scholar
  99. Tupker RA, de Monchy JG, Coenraads PJ, Homan A, and Van Der Meer JB (1996) Induction of atopic dermatitis by inhalation of house dust mite. J Allergy Clin Immunol 97:1064–1070PubMedCrossRefGoogle Scholar
  100. Valenta R, Natter S, Seiberler S, Wichlas S, Maurer D, Hess M, Pavelka M, Grote M, Ferreira F, Szepfalusi Z, Valent P, and Stingl G (1998) Molecular characterization of an autoallergen, Horn s 1, identified by serum IgE from atopic dermatitis patients. J Invest Dermatol 111:1178–1183PubMedCrossRefGoogle Scholar
  101. Valenta R, Seiberler S, Natter S, Mahler V, Mossabeb R, Ring J, and Stingl G (2000) Autoallergy: a pathogenetic factor in atopic dermatitis? J Allergy Clin Immunol 105:432–437PubMedCrossRefGoogle Scholar
  102. Van Reijsen FC, Bruijnzeel-Koomen CA, Kalthoff FS, Maggi E, Romagnani S, Westland JK, and Mudde GC (1992) Skin-derived aeroallergen-specific T-cell clones of Th2 phenotype in patients with atopic dermatitis. J Allergy Clin Immunol 90:184–193PubMedCrossRefGoogle Scholar
  103. Van Reijsen FC, Felius A, Wauters EA, Bruijnzeel-Koomen CA, and Koppelman SJ (1998) T-cell reactivity for a peanut-derived epitope in the skin of a young infant with atopic dermatitis. J Allergy Clin Immunol 101:207–209PubMedCrossRefGoogle Scholar
  104. Vestergaard C, Yoneyama H, and Matsushima K (2000) The NC/Nga mouse: a model for atopic dermatitis. Mol Med Today 6:209–210PubMedCrossRefGoogle Scholar
  105. Vestergaard C, Yoneyama H, Murai M, Nakamura K, Tamaki K, Terashima Y, Imai T, Yoshie O, Irimura T, Mizutani H, and Matsushima K (1999) Overproduction of Th2-specific chemokines in NC/Nga mice exhibiting atopic dermatitis-like lesions. J Clin Invest 104:1097–1105PubMedCrossRefGoogle Scholar
  106. Wang D, You Y, Case SM, McAllister-Lucas LM, Wang L, DiStefano PS, Nunez G, Bertin J, and Lin X (2002) A requirement for CARMA1 in TCR-induced NF-κB activation. Nat Immunol 3:830–835PubMedCrossRefGoogle Scholar
  107. Watanabe N, Tomimori Y, Saito K, Miura K, Wada A, Tsudzuki M, and Fukuda Y (2002) Chymase inhibitor improves dermatitis in NC/Nga mice. Int Arch Allergy Immunol 128:229–234PubMedCrossRefGoogle Scholar
  108. Watanabe O, Natori K, Tamari M, Shiomoto Y, Kubo S, and Nakamura Y (1999) Significantly elevated expression of PF4 (platelet factor 4) and eotaxin in the NOA mouse, a model for atopic dermatitis. J Hum Genet 44:173–176PubMedCrossRefGoogle Scholar
  109. Watanabe O, Tamari M, Natori K, Onouchi Y, Shiomoto Y, Hiraoka I, and Nakamura Y (2001) Loci on murine chromosomes 7 and 13 that modify the phenotype of the NOA mouse, an animal model of atopic dermatitis. J Hum Genet 46:221–224PubMedCrossRefGoogle Scholar
  110. Wershil BK, Wang ZS, Gordon JR, and Galli SJ (1991) Recruitment of neutrophils during IgE-dependent cutaneous late phase reactions in the mouse is mast cell-dependent. Partial inhibition of the reaction with antiserum against tumor necrosis factor-α. J Clin Invest 87:446–453PubMedCrossRefGoogle Scholar
  111. Williams CM and Galli SJ (2000) Mast cells can amplify airway reactivity and features of chronic inflammation in an asthma model in mice. J Exp Med 192:455–462PubMedCrossRefGoogle Scholar
  112. Witthuhn BA, Silvennoinen O, Miura O, Lai KS, Cwik C, Liu ET, and Ihle JN (1994) Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells. Nature 370:153–157PubMedCrossRefGoogle Scholar
  113. Wohlfahrt JG, Kunzmann S, Menz G, Kneist W, Akdis CA, Blaser K, and Schmidt-Weber CB (2003) T cell phenotype in allergic asthma and atopic dermatitis. Int Arch Allergy Immunol 131:272–282PubMedCrossRefGoogle Scholar
  114. Woodward AL, Spergel JM, Alenius H, Mizoguchi E, Bhan AK, Castigli E, Brodeur SR, Oettgen HC, and Geha RS (2001) An obligate role for T-cell receptor αβ + T cells but not T-cell receptor γδ + T cells, B cells, or CD40/CD40L interactions in a mouse model of atopic dermatitis. J Allergy Clin Immunol 107:359–366PubMedCrossRefGoogle Scholar
  115. Xiao T, Fujita H, Saeki H, Mitsui H, Sugaya M, Tada Y, Kakinuma T, Torii H, Nakamura K, Asahina A, and Tamaki K (2003) Thymus and activation-regulated chemokine (TARC/CCL17) produced by mouse epidermal Langerhans cells is upregulated by TNFα and IL-4 and downregulated by IFNγ. Cytokine 23:126–132PubMedCrossRefGoogle Scholar
  116. Yagi R, Nagai H, Iigo Y, Akimoto T, Arai T, and Kubo M (2002) Development of atopic dermatitis-like skin lesions in STAT6-deficient NC/Nga mice. J Immunol 168:2020–2027PubMedGoogle Scholar
  117. Yamanaka K, Tanaka M, Tsutsui H, Kupper TS, Asahi K, Okamura H, Nakanishi K, Suzuki M, Kayagaki N, Black RA, Miller DK, Nakashima K, Shimizu M, and Mizutani H (2000) Skin-specific caspase-1-transgenic mice show cutaneous apoptosis and pre-endotoxin shock condition with a high serum level of IL-18. J Immunol 165:997–1003PubMedGoogle Scholar
  118. Yoshimoto T, Okamura H, Tagawa YI, Iwakura Y, and Nakanishi K (1997) Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-γ production from activated B cells. Proc Natl Acad Sci USA 94:3948–3953PubMedCrossRefGoogle Scholar
  119. Yoshioka T, Hikita I, Matsutani T, Yoshida R, Asakawa M, Toyosaki-Maeda T, Hirasawa T, Suzuki R, Arimura A, and Horikawa T (2003) DS-Nh as an experimental model of atopic dermatitis induced by Staphylococcus aureus producing staphylococcal enterotoxin C. Immunology 108:562–569PubMedCrossRefGoogle Scholar
  120. Zabeau L, Gevaert P, Bachert C, and Tavernier J (2003) Interleukin-5, eosinophilic diseases and therapeutic intervention. Curr Drug Targets Inflam Allergy 2:319–328CrossRefGoogle Scholar
  121. Zou GM and Tam YK (2002) Cytokines in the generation and maturation of dendritic cells: recent advances. Eur Cytokine Netw 13:186–199PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • T. Brzoska
    • 1
  • T. A. Luger
    • 1
  1. 1.Department of Dermatology and Ludwig Boltzmann Institute for Cell- and Immunobiology of the SkinUniversity Clinics MünsterMünsterGermany

Personalised recommendations