Clinical Reviews in Allergy & Immunology

, Volume 33, Issue 3, pp 191–198 | Cite as

Cellular Aspects of Atopic Dermatitis



Atopic dermatitis (AD) is a highly pruritic, chronic, and relapsing inflammatory skin disease. Recent interest in AD has been sparked by reports of its increasing prevalence and its contribution to increasing health care costs. A precise understanding of immunologic mechanisms is crucial for the development of effective treatment strategies for AD. Various studies reveal that AD has a multifactorial cause with the activation of complex immunologic and inflammatory pathways. This review will discuss cellular-mediated immunological pathomechanisms of AD. Emphasis will be given to the role played by T cells, antigen-presenting cells, eosinophils, and keratinocytes. We also examine the immunological effect of superantigens on various inflammatory cells including T regulatory cells.


Atopic dermatitis T cell Antigen-presenting cell Eosinophil Keratinocyte Superantigens T regulatory cell 



atopic dermatitis


antigen-presenting cell


Langerhans’ cell


granulocyte–macrophage colony-stimulating factor


cutaneous lymphocyte-associated antigen




dendritic cell


high-affinity receptor for IgE


low-affinity receptor for IgE


inflammatory dendritic epidermal cell


monocyte chemoattractant protein


thymus and activation-regulated chemokine


plasmacytoid dendritic cell


major basic protein


eosinophil peroxidase


eosinophil cationic protein


eosinophil-derived neurotoxin




platelet-activating factor


monocyte chemotactic protein


tumor necrosis factor

Treg cell

T regulatory cell


  1. 1.
    Leung DY, Bieber T (2003) Atopic dermatitis. Lancet 361:151–160PubMedGoogle Scholar
  2. 2.
    Ou LS, Leung DY (2005) Advances in atopic dermatitis. Chang Gung Medical Journal 28:1–8PubMedGoogle Scholar
  3. 3.
    Spergel JM, Paller AS (2003) Atopic dermatitis and the atopic march. J Allergy Clin Immunol 112:S118–S127PubMedGoogle Scholar
  4. 4.
    Kao CC, Huang JL, Ou LS, See LC (2007) The prevalence, severity and seasonal variation of asthma, rhinitis and eczema in Taiwan schoolchildren. Pediatr Allergy Immunol (In press)Google Scholar
  5. 5.
    Bender BG, Leung SB, Leung DY (2003) Actigraphy assessment of sleep disturbance in patients with atopic dermatitis: an objective life quality measure. J Allergy Clin Immunol 111:598–602PubMedGoogle Scholar
  6. 6.
    Hamid Q, Boguniewicz M, Leung DY (1994) Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J Clin Invest 94:870–876PubMedGoogle Scholar
  7. 7.
    Allam JP, Bieber T, Novak N (2005) Recent highlights in the pathophysiology of atopic eczema. Int Arch Allergy Immunol 136:191–197PubMedGoogle Scholar
  8. 8.
    Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA (2004) New insights into atopic dermatitis. J Clin Invest 113:651–657PubMedGoogle Scholar
  9. 9.
    Toda M, Leung DY, Molet S, Boguniewicz M, Taha R, Christodoulopoulos P, Fukuda T, Elias JA, Hamid QA (2003) Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions. J Allergy Clin Immunol 111:875–881PubMedGoogle Scholar
  10. 10.
    Herz U, Bunikowski R, Renz H (1998) Role of T cells in atopic dermatitis. New aspects on the dynamics of cytokine production and the contribution of bacterial superantigens. Int Arch Allergy Immunol 115:179–190PubMedGoogle Scholar
  11. 11.
    Leung DY (2000) Atopic dermatitis: new insights and opportunities for therapeutic intervention. J Allergy Clin Immunol 105:860–876PubMedGoogle Scholar
  12. 12.
    Akdis CA, Akdis M, Trautmann A, Blaser K (2000) Immune regulation in atopic dermatitis. Curr Opin Immunol 12:641–646PubMedGoogle Scholar
  13. 13.
    Kapp A, Neuner P, Krutmann J, Luger TA, Schopf E (1991) Production of interleukin-2 by mononuclear cells in vitro in patients with atopic dermatitis and psoriasis. Comparison with serum interleukin-2 receptor levels. Acta Derm Venereol 71(5):403–406PubMedGoogle Scholar
  14. 14.
    Dworzak MN, Froschl G, Printz D, Fleischer C, Potschger U, Fritsch G, Gadner H, Emminger W (1999) Skin-associated lymphocytes in the peripheral blood of patients with atopic dermatitis: signs of subset expansion and stimulation. J Allergy Clin Immunol 103:901–906PubMedGoogle Scholar
  15. 15.
    Shimada Y, Sato S, Hasegawa M, Tedder TF, Takehara K (1999) Elevated serum l-selectin levels and abnormal regulation of l-selectin expression on leukocytes in atopic dermatitis: soluble l-selectin levels indicate disease severity. J Allergy Clin Immunol 104:163–168PubMedGoogle Scholar
  16. 16.
    Akdis M, Akdis CA, Weigl L, Disch R, Blaser K (1997) Skin-homing, CLA+ memory T cells are activated in atopic dermatitis and regulate IgE by an IL-13-dominated cytokine pattern: IgG4 counter-regulation by CLA-memory T cells. J Immunol 159:4611–4619PubMedGoogle Scholar
  17. 17.
    Akdis M, Simon HU, Weigl L, Kreyden O, Blaser K, Akdis CA (1999) Skin homing (cutaneous lymphocyte-associated antigen-positive) CD8+ T cells respond to superantigen and contribute to eosinophilia and IgE production in atopic dermatitis. J Immunol 163:466–475PubMedGoogle Scholar
  18. 18.
    Chan LS, Robinson N, 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 117:977–983PubMedGoogle Scholar
  19. 19.
    Spergel JM, Mizoguchi E, Oettgen H, Bhan AK, Geha RS (1999) Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. J Clin Invest 103:1103–1111PubMedGoogle Scholar
  20. 20.
    Santamaria Babi LF, Picker LJ, Perez Soler MT, Drzimalla K, Flohr P, Blaser K, Hauser C (1995) Circulating allergen-reactive T cells from patients with atopic dermatitis and allergic contact dermatitis express the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen. J Exp Med 181:1935–1940PubMedGoogle Scholar
  21. 21.
    Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301–314PubMedGoogle Scholar
  22. 22.
    Picker LJ, Michie SA, Rott LS, Butcher EC (1990) A unique phenotype of skin-associated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites. Am J Pathol 136:1053–1068PubMedGoogle Scholar
  23. 23.
    Leung DY, Gately M, Trumble A, Ferguson-Darnell B, Schlievert PM, Picker LJ (1995) Bacterial superantigens induce T cell expression of the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen, via stimulation of interleukin 12 production. J Exp Med 181:747–753PubMedGoogle Scholar
  24. 24.
    Trautmann A, Akdis M, Brocker EB, Blaser K, Akdis CA (2001) New insights into the role of T cells in atopic dermatitis and allergic contact dermatitis. Trends Immunol 22:530–532PubMedGoogle Scholar
  25. 25.
    Trautmann A, Akdis M, Kleemann D, Altznauer F, Simon HU, Graeve T, Noll M, Brocker EB, Blaser K, Akdis CA (2000) T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J Clin Invest 106:25–35PubMedGoogle Scholar
  26. 26.
    Trautmann A, Altznauer F, Akdis M, Simon HU, Disch R, Brocker EB, Blaser K, Akdis CA (2001) The differential fate of cadherins during T-cell-induced keratinocyte apoptosis leads to spongiosis in eczematous dermatitis. J Invest Dermatol 117:927–934PubMedGoogle Scholar
  27. 27.
    Klunker S, Trautmann A, Akdis M, Verhagen J, Schmid-Grendelmeier P, Blaser K, Akdis CA (2003) A second step of chemotaxis after transendothelial migration: keratinocytes undergoing apoptosis release IFN-gamma-inducible protein 10, monokine induced by IFN-gamma, and IFN-gamma-inducible alpha-chemoattractant for T cell chemotaxis toward epidermis in atopic dermatitis. J Immunol 171:1078–1084PubMedGoogle Scholar
  28. 28.
    Bieber T (1997) Fc epsilon RI-expressing antigen-presenting cells: new players in the atopic game. Immunol Today 18:311–313PubMedGoogle Scholar
  29. 29.
    Novak N, Kraft S, T Bieber T (2001) IgE receptors. Curr Opin Immunol 13:721–726PubMedGoogle Scholar
  30. 30.
    Novak N, Kraft S, Bieber T (2003) Unraveling the mission of FceRI on antigen-presenting cells. J Allergy Clin Immunol 111:38–44PubMedGoogle Scholar
  31. 31.
    Bieber T, de la Salle H, Wollenberg A, Hakimi J, Chizzonite R, Ring J , Hanau D, de la Salle C (1992) Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin e (fc epsilon ri). J Exp Med 175:1285–1290PubMedGoogle Scholar
  32. 32.
    Wollenberg A, Kraft S, Hanau D, Bieber T (1996) Immunomorphological and ultrastructural characterization of Langerhans cells and a novel, inflammatory dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema. J Invest Dermatol 106:446–453PubMedGoogle Scholar
  33. 33.
    Novak N, Valenta R, Bohle B, Laffer S, Haberstok J, Kraft S, Bieber T (2004) FcepsilonRI engagement of Langerhans cell-like dendritic cells and inflammatory dendritic epidermal cell-like dendritic cells induces chemotactic signals and different T-cell phenotypes in vitro. J Allergy Clin Immunol 113:949–957PubMedGoogle Scholar
  34. 34.
    Langeveld-Wildschut EG, Bruijnzeel PL, Mudde GC, Versluis C, Van Ieperen-Van Dijk AG, Bihari IC, Knol EF, Thepen T, Bruijnzeel-Koomen CA, van Reijsen FC (2000) Clinical and immunologic variables in skin of patients with atopic eczema and either positive or negative atopy patch test reactions. J Allergy Clin Immunol 105:1008–1016PubMedGoogle Scholar
  35. 35.
    Novak N, Kraft S, Haberstok J, Geiger E, Allam P, Bieber T (2002) A reducing microenvironment leads to the generation of FcepsilonRI high inflammatory dendritic epidermal cells (IDEC). J Invest Dermatol 119:842–849PubMedGoogle Scholar
  36. 36.
    Semper AE, Heron K, Woollard AC, Kochan JP, Friedmann PS, Church MK, Reischl IG (2003) Surface expression of Fc epsilon RI on Langerhans’ cells of clinically uninvolved skin is associated with disease activity in atopic dermatitis, allergic asthma, and rhinitis. J Allergy Clin Immunol 112:411–419PubMedGoogle Scholar
  37. 37.
    Laouini D, Alenius H, Bryce P, Oettgen H, Tsitsikov E, Geha RS (2003) IL-10 is critical for Th2 responses in a murine model of allergic dermatitis. J Clin Invest 112:1058–1066PubMedGoogle Scholar
  38. 38.
    Novak N, Bieber T, Katoh N (2001) Engagement of Fc epsilon RI on human monocytes induces the production of IL-10 and prevents their differentiation in dendritic cells. J Immunol 167:797–804PubMedGoogle Scholar
  39. 39.
    Kerschenlohr K, Decard S, Darsow U, Ollert M, Wollenberg A (2003) Clinical and immunologic reactivity to aeroallergens in “intrinsic” atopic dermatitis patients. J Allergy Clin Immunol 111:195–197PubMedGoogle Scholar
  40. 40.
    Oppel T, Schuller E, Gunther S, Moderer M, Haberstok J, Bieber T, Wollenberg A (2000) Phenotyping of epidermal dendritic cells allows the differentiation between extrinsic and intrinsic forms of atopic dermatitis. Br J Dermatol 143:1193–1198PubMedGoogle Scholar
  41. 41.
    Novak N, Bieber T, Leung DY (2003) Immune mechanisms leading to atopic dermatitis. J Allergy Clin Immunol 112:S128–S139PubMedGoogle Scholar
  42. 42.
    Wollenberg A, Wagner M, Gunther S, Towarowski A, Tuma E, Moderer M, Rothenfusser S, Wetzel S, Endres S, Hartmann G (2002) Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. J Invest Dermatol 119:1096–1102PubMedGoogle Scholar
  43. 43.
    Novak N, Allam JP, Hagemann T, Jenneck C, Laffer S, Valenta R, Kochan J, Bieber T (2004) Characterization of FcepsilonRI-bearing CD123 blood dendritic cell antigen-2 plasmacytoid dendritic cells in atopic dermatitis. J Allergy Clin Immunol 114:364–370PubMedGoogle Scholar
  44. 44.
    Kato M, Kephart GM, Talley NJ, Wagner JM, Sarr MG, Bonno M, McGovern TW, Gleich GJ (1998) Eosinophil infiltration and degranulation in normal human tissue. Anat Rec 252:418–425PubMedGoogle Scholar
  45. 45.
    Straumann A, Simon HU (2004) The physiological and pathophysiological roles of eosinophils in the gastrointestinal tract. Allergy 59:15–25PubMedGoogle Scholar
  46. 46.
    Kagi MK, Joller-Jemelka H, Wuthrich B (1992) Correlation of eosinophils, eosinophil cationic protein and soluble interleukin-2 receptor with the clinical activity of atopic dermatitis. Dermatology 185:88–92PubMedCrossRefGoogle Scholar
  47. 47.
    Kiehl P, Falkenberg K, Vogelbruch M, Kapp A (2001) Tissue eosinophilia in acute and chronic atopic dermatitis: a morphometric approach using quantitative image analysis of immunostaining. Br J Dermatol 145:720–729PubMedGoogle Scholar
  48. 48.
    Breuer K, Kapp A, Werfel T (2001) Urine eosinophil protein X (EPX) is an in vitro parameter of inflammation in atopic dermatitis of the adult age. Allergy 56:780–784PubMedGoogle Scholar
  49. 49.
    Gleich GJ, Adolphson CR, Leiferman KM (1993) The biology of the eosinophilic leukocyte. Annu Rev Med 44:85–101PubMedGoogle Scholar
  50. 50.
    Minnicozzi M, Duran WN, Gleich GJ, Egan RW (1994) Eosinophil granule proteins increase microvascular macromolecular transport in the hamster cheek pouch. J Immunol 153:2664–2670PubMedGoogle Scholar
  51. 51.
    Gleich GJ, Schroeter AL, Marcoux JP, Sachs MI, O’Connell EJ, Kohler PF (1984) Episodic angioedema associated with eosinophilia. N Engl J Med 310:1621–1626PubMedCrossRefGoogle Scholar
  52. 52.
    Czech W, Krutmann J, Schopf E, Kapp A (1992) Serum eosinophil cationic protein (ECP) is a sensitive measure for disease activity in atopic dermatitis. Br J Dermatol 126:351–355PubMedGoogle Scholar
  53. 53.
    Huang JL, Chen LC, Kuo ML (2000) The changes of serum levels interleukin-2, intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1 and Th1 and Th2 in severe atopic dermatitis after intravenous immunoglobulin therapy. Ann Allergy Asthma Immunol 84:345–352PubMedCrossRefGoogle Scholar
  54. 54.
    Taniuchi S, Chihara J, Kojima T, Yamamoto A, Sasai M, Kobayashi Y (2001) Serum eosinophil derived neurotoxin may reflect more strongly disease severity in childhood atopic dermatitis than eosinophil cationic protein. J Dermatol Sci 26:79–82PubMedGoogle Scholar
  55. 55.
    Wassom DL, Loegering DA, Solley GO, Moore SB, Schooley RT, Fauci AS, Gleich GJ (1981) Elevated serum levels of the eosinophil granule major basic protein in patients with eosinophilia. J Clin Invest 67:651–661PubMedGoogle Scholar
  56. 56.
    Oymar K, Bjerknes R (2000) Urinary eosinophil protein X in children with atopic dermatitis: relation to atopy and disease activity. Allergy 55:964–968PubMedGoogle Scholar
  57. 57.
    Leiferman KM, Ackerman SJ, Sampson HA, Haugen HS, Venencie PY, Gleich GJ (1985) Dermal deposition of eosinophil-granule major basic protein in atopic dermatitis. Comparison with onchocerciasis. N Engl J Med 313:282–285PubMedCrossRefGoogle Scholar
  58. 58.
    Lee T, Lenihan DJ, Malone B, Roddy LL, Wasserman SI (1984) Increased biosynthesis of platelet-activating factor in activated human eosinophils. J Biol Chem 259:5526–5530PubMedGoogle Scholar
  59. 59.
    Shaw RJ, Walsh GM, Cromwell O, Moqbel R, Spry CJ, Kay AB (1985) Activated human eosinophils generate SRS-A leukotrienes following IgG-dependent stimulation. Nature 316:150–152PubMedGoogle Scholar
  60. 60.
    Silberstein DS, Austen KF, Owen WF Jr (1989) Hemopoietins for eosinophils. Glycoprotein hormones that regulate the development of inflammation in eosinophilia-associated disease. Hematol Oncol Clin North Am 3:511–533PubMedGoogle Scholar
  61. 61.
    Yamaguchi Y, Hayashi Y, Sugama Y, Miura Y, Kasahara T, Kitamura S, Torisu M, Mita S, Tominaga A, Takatsu K (1988) Highly purified murine interleukin 5 (IL-5) stimulates eosinophil function and prolongs in vitro survival. IL-5 as an eosinophil chemotactic factor. J Exp Med 167:1737–1742PubMedGoogle Scholar
  62. 62.
    Nishinakamura R, Miyajima A, Mee PJ, Tybulewicz VL, Murray R (1996) Hematopoiesis in mice lacking the entire granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5 functions. Blood 88:2458–2464PubMedGoogle Scholar
  63. 63.
    Dubois GR, Schweizer RC, Versluis C, Bruijnzeel-Koomen CA, Bruijnzeel PL (1998) Human eosinophils constitutively express a functional interleukin-4 receptor: interleukin-4-induced priming of chemotactic responses and induction of PI-3 kinase activity. Am J Respir Cell Mol Biol 19:691–699PubMedGoogle Scholar
  64. 64.
    Atsuta J, Fujisawa T, Iguchi K, Terada A, Kamiya H, Sakurai M (1995) Inhibitory effect of transforming growth factor beta 1 on cytokine-enhanced eosinophil survival and degranulation. Int Arch Allergy Immunol 108:31–35PubMedCrossRefGoogle Scholar
  65. 65.
    Simon D, Braathen LR, Simon HU (2004) Eosinophils and atopic dermatitis. Allergy 59:561–570PubMedGoogle Scholar
  66. 66.
    Kaplan AP, Kuna P, Reddigari SR (1995) Chemokines and the allergic response. Exp Dermatol 4:260–265PubMedGoogle Scholar
  67. 67.
    Schroder JM, Noso N, Sticherling M, Christophers E (1996) Role of eosinophil-chemotactic C–C chemokines in cutaneous inflammation. J Leukoc Biol 59:1–5PubMedGoogle Scholar
  68. 68.
    Yao TC, Kuo ML, See LC, Chen LC, Yan DC, Ou LS, Huang JL (2003) RANTES promoter polymorphism, a genetic risk factor for near-fatal asthma in Chinese children. J Allergy Clin Immunol 111:1285–1292PubMedGoogle Scholar
  69. 69.
    Bartels J, Schluter C, Richter E, Noso N, Kulke R, Christophers E, Schroder JM (1996) Human dermal fibroblasts express eotaxin: molecular cloning, mRNA expression, and identification of eotaxin sequence variants. Biochem Biophys Res Commun 225:1045–1051PubMedGoogle Scholar
  70. 70.
    Yamada H, Matsukura M, Yudate T, Chihara J, Stingl G, Tezuka T (1997) Enhanced production of RANTES, an eosinophil chemoattractant factor, by cytokine-stimulated epidermal keratinocytes. Int Arch Allergy Immunol 114:28–32PubMedGoogle Scholar
  71. 71.
    Rothenberg ME, MacLean JA, Pearlman E, Luster AD, Leder P (1997) Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia. J Exp Med 185:785–790PubMedGoogle Scholar
  72. 72.
    Ying S, Taborda-Barata L, Meng Q, Humbert M, Kay AB (1995) The kinetics of allergen-induced transcription of messenger RNA for monocyte chemotactic protein-3 and RANTES in the skin of human atopic subjects: relationship to eosinophil, T cell, and macrophage recruitment. J Exp Med 181:2153–2159PubMedGoogle Scholar
  73. 73.
    Gonzalo JA, Lloyd CM, Wen D, Albar JP, Wells TN, Proudfoot A, Martinez-A C, Dorf M, Bjerke T, Coyle AJ, Gutierrez-Ramos JC (1998) The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness. J Exp Med 188:157–167PubMedGoogle Scholar
  74. 74.
    Dombrowicz D, Capron M (2001) Eosinophils, allergy and parasites. Curr Opin Immunol 13:716–720PubMedGoogle Scholar
  75. 75.
    Ponath PD, Qin S, Post TW, Wang J, Wu L, Gerard NP, Newman W, Gerard C, Mackay CR (1996) Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. J Exp Med 183:2437–2448PubMedGoogle Scholar
  76. 76.
    Homey B, Zlotnik A (1999) Chemokines in allergy. Curr Opin Immunol 11:626–634PubMedGoogle Scholar
  77. 77.
    Girolomoni G, Pastore S (2001) The role of keratinocytes in the pathogenesis of atopic dermatitis. J Am Acad Dermatol 45:S25–S28PubMedGoogle Scholar
  78. 78.
    Pastore S, Mascia F, Giustizieri ML, Giannetti A, Girolomoni G (2000) Pathogenetic mechanisms of atopic dermatitis. Arch Immunol Ther Exp (Warsz) 48:497–504Google Scholar
  79. 79.
    Pastore S, Fanales-Belasio E, Albanesi C, Chinni LM, Giannetti A, Girolomoni G (1997) Granulocyte macrophage colony-stimulating factor is overproduced by keratinocytes in atopic dermatitis. Implications for sustained dendritic cell activation in the skin. J Clin Invest 99:3009–3017PubMedGoogle Scholar
  80. 80.
    Pastore S, Corinti S, La Placa M, Didona B, Girolomoni G (1998) Interferon-gamma promotes exaggerated cytokine production in keratinocytes cultured from patients with atopic dermatitis. J Allergy Clin Immunol 101:538–544PubMedGoogle Scholar
  81. 81.
    Albanesi C, Cavani A, Girolomoni G (1999) IL-17 is produced by nickel-specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN-gamma and TNF-alpha. J Immunol 162:494–502PubMedGoogle Scholar
  82. 82.
    Bratton DL, Hamid Q, Boguniewicz M, Doherty DE, Kailey JM, Leung DY (1995) Granulocyte macrophage colony-stimulating factor contributes to enhanced monocyte survival in chronic atopic dermatitis. J Clin Invest 95:211–218PubMedGoogle Scholar
  83. 83.
    Albanesi C, Pastore S, Fanales-Belasio E, Girolomoni G (1998) Cetirizine and hydrocortisone differentially regulate ICAM-1 expression and chemokine release in cultured human keratinocytes. Clin Exp Allergy 28:101–109PubMedGoogle Scholar
  84. 84.
    Campbell JJ, Haraldsen G, Pan J, Rottman J, Qin S, Ponath P, Andrew DP, Warnke R, Ruffing N, Kassam N, Wu L, Butcher EC (1999) The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells. Nature 400:776–780PubMedGoogle Scholar
  85. 85.
    Imai T, Nagira M, Takagi S, Kakizaki M, Nishimura M, Wang J, Gray PW, Matsushima K, 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 11:81–88PubMedGoogle Scholar
  86. 86.
    Vestergaard C, Bang K, Gesser B, Yoneyama H, Matsushima K, Larsen CG (2000) A Th2 chemokine, TARC, produced by keratinocytes may recruit CLA+CCR4+ lymphocytes into lesional atopic dermatitis skin. J Invest Dermatol 115:640–646PubMedGoogle Scholar
  87. 87.
    Giustizieri ML, Mascia F, Frezzolini A, De Pita O, Chinni LM, Giannetti A, Girolomoni G, Pastore S (2001) Keratinocytes from patients with atopic dermatitis and psoriasis show a distinct chemokine production profile in response to T cell-derived cytokines. J Allergy Clin Immunol 107:871–877PubMedGoogle Scholar
  88. 88.
    Taha RA, Minshall EM, Leung DY, Boguniewicz M, Luster A, Muro S, Toda M, Hamid QA (2000) Evidence for increased expression of eotaxin and monocyte chemotactic protein-4 in atopic dermatitis. J Allergy Clin Immunol 105:1002–1007PubMedGoogle Scholar
  89. 89.
    Gallo RL, Murakami M, Ohtake T, Zaiou M (2002) Biology and clinical relevance of naturally occurring antimicrobial peptides. J Allergy Clin Immunol 110:823–831PubMedGoogle Scholar
  90. 90.
    Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY (2002) Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 347:1151–1160PubMedGoogle Scholar
  91. 91.
    Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, Darst MA, Gao B, Boguniewicz M, Travers JB, Leung DY (2003) Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevent induction of innate immune response genes. J Immunol 171:3262–3269PubMedGoogle Scholar
  92. 92.
    Leyden JJ, Marples RR, Kligman AM (1974) Staphylococcus aureus in the lesions of atopic dermatitis. Br J Dermatol 90:525–530PubMedGoogle Scholar
  93. 93.
    Hauser C, Wuethrich B, Matter L, Wilhelm JA, Sonnabend W, Schopfer K (1985) Staphylococcus aureus skin colonization in atopic dermatitis patients. Dermatologica 170:35–69PubMedGoogle Scholar
  94. 94.
    Kotzin BL, Leung DY, Kappler J, Marrack P (1993) Superantigens and their potential role in human disease. Adv Immunol 54:99–166PubMedGoogle Scholar
  95. 95.
    Laouini D, Kawamoto S, Yalcindag A, Bryce P, Mizoguchi E, Oettgen H, Geha RS (2003) Epicutaneous sensitization with superantigen induces allergic skin inflammation. J Allergy Clin Immunol 112:981–987PubMedGoogle Scholar
  96. 96.
    Leung DY, Harbeck R, Bina P, Reiser RF, Yang E, Norris DA, Hanifin JM, 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
  97. 97.
    Breuer K, Wittmann M, Bosche B, Kapp A, Werfel T (2000) Severe atopic dermatitis is associated with sensitization to staphylococcal enterotoxin B (SEB). Allergy 55:551–555PubMedGoogle Scholar
  98. 98.
    Bunikowski R, Mielke ME, Skarabis H, Worm M, Anagnostopoulos I, Kolde G, Wahn U, Renz H (2000) Evidence for a diseasepromoting effect of Staphylococcus aureus-derived exotoxins in atopic dermatitis. J Allergy Clin Immunol 105:814–819PubMedGoogle Scholar
  99. 99.
    Strickland I, Hauk PJ, Trumble AE, Picker LJ, Leung DY (1999) Evidence for superantigen involvement in skin homing of T cells in atopic dermatitis. J Invest Dermatol 112:249–253PubMedGoogle Scholar
  100. 100.
    Cho SH, Strickland I, Tomkinson A, Fehringer AP, Gelfand EW, Leung DY (2001) Preferential binding of Staphylococcus aureus to skin sites of Th2-mediated inflammation in a murine model. J Invest Dermatol 116:658–663PubMedGoogle Scholar
  101. 101.
    Cho SH, Strickland, Boguniewicz M, Leung DY (2001) Fibronectin and fibrinogen contribute to the enhanced binding of Staphylococcus aureus to atopic skin. J Allergy Clin Immunol 108:269–274PubMedGoogle Scholar
  102. 102.
    Michie CA, Davis T (1996) Atopic dermatitis and staphylococcal superantigens. Lancet 347:324PubMedGoogle Scholar
  103. 103.
    Li LB, Goleva E, Hall CF, Ou LS, Leung DY (2004) Superantigen-induced corticosteroid resistance of human T cells occurs through activation of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK-ERK) pathway. J Allergy Clin Immunol 114:1059–1069PubMedGoogle Scholar
  104. 104.
    Suto A, Nakajima H, Kagami SI, Suzuki K, Saito Y, Iwamoto I (2001) Role of CD4(+) CD25(+) regulatory T cells in T helper 2 cell-mediated allergic inflammation in the airways. Am J Respir Crit Care Med 15(164):680–687Google Scholar
  105. 105.
    Chatila TA, Blaeser F, Ho N, Lederman HM, Voulgaropoulos C, Helms C, Bowcock AM (2000) JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J Clin Invest 106:R75–R81PubMedGoogle Scholar
  106. 106.
    Ou LS, Goleva E, Hall C, Leung DY (2004) T regulatory cells in atopic dermatitis and subversion of their activity by superantigens. J Allergy Clin Immunol 113:756–763PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  1. 1.Division of Allergy, Asthma and Rheumatology Department of PediatricsChang Gung Children’s Hospital, Chang Gung UniversityTaoyuanRepublic of China

Personalised recommendations