The role of leukocytes, keratinocytes, and allergen-specific IgE in the development of atopic dermatitis

Journal of Investigative Dermatology

Volumn 129, Issue 8, 2009, Pages 1878-1891

  Werfel, Thomas ^a  

^a HANNOVER MEDICAL SCHOOL   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL ANTIGEN; FOOD ALLERGEN; IMMUNOGLOBULIN E; INTERLEUKIN 13; INTERLEUKIN 31; INTERLEUKIN 4;

ADAPTIVE IMMUNITY; ATOPIC DERMATITIS; AUTOIMMUNITY; BONE MARROW CELL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL INTERACTION; DANDER; DENDRITIC CELL; DERMATOPHAGOIDES; DISEASE SEVERITY; ECZEMA; EOSINOPHIL; HUMAN; IMMUNE DEFICIENCY; IMMUNOHISTOLOGY; INFECTION SENSITIVITY; INFLAMMATION; INNATE IMMUNITY; KERATINOCYTE; LEUKOCYTE; MOULD; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; SKIN INFECTION; TH1 CELL; TH17 CELL; TH2 CELL; WEED;

EID: 67651124902     PISSN: 0022202X     EISSN: 15231747     Source Type: Journal    
DOI: 10.1038/jid.2009.71     Document Type: Article

References (152)

1. Abernathy-Carver KJ, Sampson HA, Picker LJ, Leung DY (1995) Milk-induced eczema is associated with the expansion of T-cells expressing cutaneous lymphocyte antigen. J Clin Invest 95:913-8
2. Ahmad-Nejad P, Mrabet-Dahbi S, Breuer K, Klotz M, Werfel T, Herz U et al. (2004) The tolllike receptor 2 R753Q polymorphism defines a subgroup of patients with atopic dermatitis having severe phenotype. J Allergy Clin Immunol 113:565-7
3. Akdis CA, Akdis M, Bieber T, Bindslev-Jensen C, Boguniewicz M, Eigenmann P et al. (2006) Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report. J Allergy Clin Immunol 118:152-69 and Allergy 61: 969-87
4. 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: 4611-9
5. Akdis M, Blaser K, Akdis CA (2005) T regulatory cells in allergy: novel concepts in the pathogenesis, prevention, and treatment of allergic diseases. J Allergy Clin Immunol 116:961-8
6. 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 163:466-75
7. Akkoc T, de Koning PJ, Rü ckert B, Barlan I, Akdis M, Akdis CA (2008) Increased activationinduced cell death of high IFN-gammaproducing T(H)1 cells as a mechanism of T(H)2 predominance in atopic diseases. J Allergy Clin Immunol. 121:652-8
8. Albanesi C, Scarponi C, Sebastiani S, Cavani A, Federici M, De Pita O et al. (2000) IL-4 enhances keratinocyte expression of CXCR3 agonistic chemokines. J Immunol 165:1395-402
9. Albanesi C, Scarponi C, Sebastiani S, Cavani A, Federici M, Sozzani S et al. (2001) A cytokine-to-chemokine axis between T-lymphocytes and keratinocytes can favor Th-1 cell accumulation in chronic inflammatory skin diseases. J Leukoc Biol 70:617-23
10. Allakhverdi Z, Comeau MR, Jessup HK, Yoon BR, Brewer A, Chartier S et al. (2007) Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells. J Exp Med 204:253-8
11. Beck LA, Saini S (2006) Wanted: A study with omalizumab to determine the role of IgEmediated pathways in atopic dermatitis. J Am Acad Dermatol 55:540-1
12. Belloni B, Ziai M, Lim A, Lemercier B, Sbornik M, Weidinger S et al. (2007) Low-dose anti-IgE therapy in patients with atopic eczema with high serum IgE levels. J Allergy Clin Immunol. 120:1223-5
13. Bieber T (2007) The pro- and anti-inflammatory properties of human antigen-presenting cells expressing the high affinity receptor for IgE (Fc epsilon RI). Immunobiology 212:499-503
14. Bieber T (2008) Atopic dermatitis. N Engl J Med 358:1483-94
15. Biedermann T, Lametschwandtner G, Tangemann K, Kund J, Hinteregger S, Carballido-Perrig N et al. (2006) IL-12 instructs skin homing of human Th2 cells. J Immunol 177:3763-70
16. Bilsborough J, Leung DY, Maurer M, Howell M, Boguniewicz M, Yao L et al. (2006) IL-31 is associated with cutaneous lymphocyte antigen- positive skin homing T-cells in patients with atopic dermatitis. J Allergy Clin Immunol 117:418-25
17. Bohle B, Zwolfer B, Heratizadeh A, Jahn-Schmid B, Antonia YD, Alter M et al. (2006) Cooking birch pollen-related food: divergent consequences for IgE- and T-cell-mediated reactivity in vitro and in vivo. J Allergy Clin Immunol 118:242-9
18. Breuer K, Haeussler S, Kapp A, Werfel T (2002) Staphylococcus aureus: colonizing features and influence of an antibacterial treatment in adults with atopic dermatitis. Br J Dermatol 147:55-61
19. Breuer K, Wittmann M, Bosche B, Kapp A, Werfel T (2000) Severe atopic dermatitis is associated with sensitization to staphylococcal enterotoxin B (SEB). Allergy 55:551-5
20. Breuer K, Wulf A, Constien A, Tetau D, Kapp A, Werfel T (2004) Birch pollen-related food as a provocation factor of allergic symptoms in children with atopic eczema/dermatitis syndrome. Allergy 59:988-94
21. Brown SJ, McLean WHI (2009) Eczema genetics: current state of knowledge and future goals. J Invest Dermatol 129:543-52
22. Bruijnzeel-Koomen C, Storz E, Menz G, Bruijnzeel P (1992) Skin eosinophilia in patients with allergic and nonallergic asthma and atopic dermatitis. J Allergy Clin Immunol 89:52-9
23. Bunikowski R, Mielke M, Skarabis H, Herz U, Bergmann RL, Wahn U et al. (1999) Prevalence and role of serum IgE antibodies to the Staphylococcus aureus-derived superantigens SEA and SEB in children with atopic dermatitis. J Allergy Clin Immunol 103:119-24
24. Bussmann C, Bockenhoff A, Henke H, Werfel T, Novak N (2006) Does allergen-specific immunotherapy represent a therapeutic option for patients with atopic dermatitis? J Allergy Clin Immunol 118:1292-8
25. Bussmann C, Maintz L, Hart J, Allam JP, Vrtala S, Chen KW et al. (2007) Clinical improvement and immunological changes in atopic dermatitis patients undergoing subcutaneous immunotherapy with a house dust mite allergoid: a pilot study. Clin Exp Allergy 37:1277-85
26. Cardona ID, Goleva E, Ou LS, Leung DY (2006) Staphylococcal enterotoxin B inhibits regulatory T-cells by inducing glucocorticoidinduced TNF receptor-related protein ligand on monocytes. J Allergy Clin Immunol 117:688-95
27. Casagrande BF, Fluckiger S, Linder MT, Johansson C, Scheynius A, Crameri R et al. (2006) Sensitization to the yeast Malassezia sympodialis is specific for extrinsic and intrinsic atopic eczema. J Invest Dermatol 126:2414-21
28. Darsow U, Laifaoui J, Kerschenlohr K, Wollenberg A, Przybilla B, Wuthrich B et al. (2004) The prevalence of positive reactions in the atopy patch test with aeroallergens and food allergens in subjects with atopic eczema: a European multicenter study. Allergy 59:1318-25
29. De Benedetto A, Agnihothri R, McGirt LY, Bankova LG, Beck LA (2009) Atopic dermatitis: a disease caused by innate immune defects? J Invest Dermatol 129:14-30
30. Demehri S, Liu Z, Lee J, Lin MH, Crosby SD, Roberts CJ et al. (2008) Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP a sentinel for epidermal integrity. PLoS Biol 27:6-e123
31. Dijkstra D, Leurs R, Chazot P, Shenton FC, Stark H, Werfel T et al. (2007) Histamine downregulates monocyte CCL2 production through the histamine H4 receptor. J Allergy Clin Immunol 120:300-7
32. Dinarello CA (2007) Interleukin-18 and the pathogenesis of inflammatory diseases. Semin Nephrol 27:98-114
33. Elsner J, Kapp A (1999) Regulation and modulation of eosinophil effector functions. Allergy 54:15-26
34. Fiset PO, Leung DY, Hamid Q (2006) Immunopathology of atopic dermatitis. J Allergy Clin Immunol 118:287-90
35. Forman SB, Garrett AB (2007) Success of omalizumab as monotherapy in adult atopic dermatitis: case report and discussion of the high-affinity immunoglobulin E receptor, FcepsilonRI. Cutis 80:38-40
36. Franz B, Fritzsching B, Riehl A, Oberle N, Klemke CD, Sykora J et al. (2007) Low number of regulatory T cells in skin lesions of patients with cutaneous lupus erythematosus. Arthritis Rheum 56:1910-20
37. Giustizieri ML, Albanesi C, Fluhr J, Gisondi P, Norgauer J, Girolomoni G (2004) H1 histamine receptor mediates inflammatory responses in human keratinocytes. J Allergy Clin Immunol 114:1176-82
38. Gombert M, Dieu-Nosjean MC, Winterberg F, Bunemann E, Kubitza RC, Da Cunha L et al. (2005) CCL1-CCR8 interactions: an axis mediating the recruitment of T-cells and Langerhans-type dendritic cells to sites of atopic skin inflammation. J Immunol 174:5082-91
39. Grewe M, Walther S, Gyufko K, Czech W, Schopf E, Krutmann J (1995) Analysis of the cytokine pattern expressed in situ in inhalant allergen patch test reactions of atopic dermatitis patients. J Invest Dermatol 105:407-10
40. Gutzmer R, Diestel C, Mommert S, Kother B, Stark H, Wittmann M et al. (2005) Histamine H4 receptor stimulation suppresses IL-12p70 production and mediates chemotaxis in human monocyte-derived dendritic cells. J Immunol 174:5224-32
41. Gutzmer R, Mommert S, Gschwandtner M, Zwingmann K, Stark H, Werfel T (2009) The histamine H4 receptor is functionally expressed on T(H)2 cells. J Allergy Clin Immunol 123:619-25
42. Hamid Q, Boguniewicz M, Leung DY (1994) Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J Clin Invest 94:870-6
43. Hamid Q, Naseer T, Minshall EM, Song YL, Boguniewicz M, Leung DY (1996) In vivo expression of IL-12 and IL-13 in atopic dermatitis. J Allergy Clin Immunol 98:225-31
44. Han GW, Iwatsuki K, Inoue M, Matsui T, Nishibu A, Akiba H et al. (1999) Interleukin-15 is not a constitutive cytokine in the epidermis, but is inducible in culture or inflammatory conditions. Acta Derm Venereol. 79:37-40
45. Hasannejad H, Takahashi R, Kimishima M, Hayakawa K, Shiohara T (2007) Selective impairment of Toll-like receptor 2-mediated proinflammatory cytokine production by monocytes from patients with atopic dermatitis. J Allergy Clin Immunol 120:69-75
46. He R, Oyoshi MK, Jin H, Geha RS (2007) Epicutaneous antigen exposure induces a Th-17 response that drives airway inflammation after inhalation challenge. Proc Natl Acad Sci U S A 104:15817-22
47. Hennino A, Vocanson M, Toussaint Y, Rodet K, Benetiere J, Schmitt AM et al. (2007) Skininfiltrating CD8+ T-cells initiate atopic dermatitis lesions. J Immunol 178:5571-7
48. Hoechstetter R, Dobos G, Kimmig D, Dulkys Y, Kapp A, Elsner J (2000) The CC chemokine receptor 3 CCR3 is functionally expressed on eosinophils but not on neutrophils. Eur J Immunol 30:2759-64
49. Holgate ST (2007) The epithelium takes centre stage in asthma and atopic dermatitis. Trends Immunol 28:248-51
50. Holm L, Bengtsson A, Hage-Hamsten M, Ohman S, Scheynius A (2001) Effectiveness of occlusive bedding in the treatment of atopic dermatitis-a placebo-controlled trial of 12 months' duration. Allergy 56:152-8
51. Homey B, Alenius H, Muller A, Soto H, Bowman EP, Yuan W et al. (2002) CCL27-CCR10 interactions regulate T-cell-mediated skin inflammation. Nat Med 8:157-65
52. Homey B, Steinhoff M, Ruzicka T, Leung DY (2006) Cytokines and chemokines orchestrate atopic skin inflammation. J Allergy Clin Immunol 118:178-89
53. Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, Debenedetto A et al. (2007) Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol 120:150-5
54. Howell MD, Wollenberg A, Gallo RL, Flaig M, Streib JE, Wong C et al. (2006) Cathelicidin deficiency predisposes to eczema herpeticum. J Allergy Clin Immunol 117:836-41
55. Hunter CA (2005) New IL-12-family members: IL- 23 and IL-27, cytokines with divergent functions. Nat Rev Immunol 5:521-31
56. Ito T, Wang YH, Duramad O, Hori T, Delespesse GJ, Watanabe N et al. (2005) TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med 202:1213-23
57. Jutel M, Watanabe T, Klunker S, Akdis M, Thomet OA, Malolepszy J et al. (2001) Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature 413:420-5
58. Kapp A (1993) The role of eosinophils in the pathogenesis of atopic dermatitis-eosinophil granule proteins as markers of disease activity. Allergy 48:1-5
59. Kerschenlohr K, Decard S, Przybilla B, Wollenberg A (2003) Atopy patch test reactions show a rapid influx of inflammatory dendritic epidermal cells in patients with extrinsic atopic dermatitis and patients with intrinsic atopic dermatitis. J Allergy Clin Immunol 111:869-74
60. Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura Y (2008) Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol. 128:2625-30
61. Lane JE, Cheyney JM, Lane TN, Kent DE, Cohen DJ (2006) Treatment of recalcitrant atopic dermatitis with omalizumab. J Am Acad Dermatol 54:68-72
62. Langer K, Breuer K, Kapp A, Werfel T (2007) Staphylococcus aureus-derived enterotoxins enhance house dust mite-induced patch test reactions in atopic dermatitis. Exp Dermatol 16:124-9
63. 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. 313:282-5
64. Leung AK, Hon KL, Robson WL (2007) Atopic dermatitis. Adv Pediatr 54:241-73
65. Leung DY, Bhan AK, Schneeberger EE, Geha RS (1983) Characterization of the mononuclear cell infiltrate in atopic dermatitis using monoclonal antibodies. J Allergy Clin Immunol 71:47-56
66. Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA (2004) New insights into atopic dermatitis. J Clin Invest 113:651-7
67. Li XM, Kleiner G, Huang CK, Lee SY, Schofield B, Soter NA et al. (2001) Murine model of atopic dermatitis associated with food hypersensitivity. J Allergy Clin Immunol 107:693-702
68. Maintz L, Novak N (2007) Getting more and more complex: the pathophysiology of atopic eczema. Eur J Dermatol 17:267-83
69. McGirt LY, Beck LA (2006) Innate immune defects in atopic dermatitis. J Allergy Clin Immunol 118:202-8
70. Mehl A, Verstege A, Staden U, Kulig M, Nocon M, Beyer K et al. (2005) Utility of the ratio of food-specific IgE/total IgE in predicting symptomatic food allergy in children. Allergy 60:1034-9
71. Mothes N, Niggemann B, Jenneck C, Hagemann T, Weidinger S, Bieber T et al. (2005) The cradle of IgE autoreactivity in atopic eczema lies in early infancy. J Allergy Clin Immunol 116:706-9
72. Mrabet-Dahbi S, Dalpke A, Frey M, Niehbuhr M, Draing C, Brand S et al. (2008) The toll-like receptor 2 (TRL-2) R753Q mutation modifies cytokine production and TLR expression in atopic dermatitis. J Allergy Clin Immunol 121:1013-9
73. Neis MM, Peters B, Dreuw A, Wenzel J, Bieber T, Mauch C et al. (2006) Enhanced expression levels of IL-31 correlate with IL-4 and IL-13 in atopic and allergic contact dermatitis. J Allergy Clin Immunol 118:930-7
74. Niebuhr M, Langnickel J, Draing C, Renz H, Kapp A, Werfel T (2008) 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 63:728-34
75. Niebuhr M, Lutat C, Sigel S, Werfel T (2009) Impaired TLR-2 expression and TLR-2 mediated cytokine secretion in macrophages from patients with atopic dermatitis. Allergy (in press)
76. Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF et al. (2003) Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol 171:3262-9
77. Novak N, Allam JP, Bieber T (2003) Allergic hyperreactivity to microbial components: a trigger factor of "intrinsic" atopic dermatitis? J Allergy Clin Immunol 112:215-6
78. Novak N, Bieber T (2003) Allergic and nonallergic forms of atopic diseases. J Allergy Clin Immunol 112:252-62
79. Novak N, Peng W, Yu C (2007) Network of myeloid and plasmacytoid dendritic cells in atopic dermatitis. Adv Exp Med Biol 601:97-104
80. Novak N, Valenta R, Bohle B, Laffer S, Haberstok J, Kraft S et al. (2004) Fc epsilon RI 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 113:949-57
81. Novembre E, Cianferoni A, Lombardi E, Bernardini R, Pucci N, Vierucci A (2001) Natural history of "intrinsic" atopic dermatitis. Allergy 56:452-3
82. Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T et al. (2002) Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 347:1151-60
83. O'Regan GM, Irvine AD (2008) The role of filaggrin loss-of-function mutations in atopic dermatitis. Curr Opin Allergy Clin Immunol 8:406-10
84. Oosting AJ, Bruin-Weller MS, Terreehorst I, Tempels-Pavlica Z, Aalberse RC, de Monchy JG et al. (2002) Effect of mattress encasings on atopic dermatitis outcome measures in a double-blind, placebo-controlled study: the Dutch mite avoidance study. J Allergy Clin Immunol 110:500-6
85. 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 113:756-63
86. Pajno GB, Caminiti L, Vita D, Barberio G, Salzano G, Lombardo F et al. (2007) Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a randomized, double-blind, placebo-controlled study. J Allergy Clin Immunol 120:164-70
87. Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP et al. (2006) Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38:441-6
88. Giustizieri ML, Mascia F, Frezzolini A, De Pità O, Chinni LM, Giannetti A et al. (2001) Keratinocytes from patients with atopic dermatitis and psoriasis show a distinct chemokine production profile in response to T cellderived cytokines. J Allergy Clin Immunol 107:871-7
89. 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 101:538-44
90. Pastore S, Giustizieri ML, Mascia F, Giannetti A, Kaushansky K, Girolomoni G. (2000) Dysregulated activation of activator protein 1 in keratinocytes of atopic dermatitis patients with enhanced expression of granulocyte/ macrophage-colony stimulating factor. J Invest Dermatol 115:1134-43
91. 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 136:1053-68
92. Piskin G, Sylva-Steenland RM, Bos JD, Teunissen MB (2006) In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin. J Immunol 176:1908-15
93. Purwar R, Kraus M, Werfel T, Wittmann M (2007a) Modulation of Keratinocyte-Derived MMP-9 by IL-13: A Possible Role for the Pathogenesis of Epidermal Inflammation. J Invest Dermatol 128:59-66
94. Purwar R, Werfel T, Wittmann M (2006) IL-13- stimulated human keratinocytes preferentially attract CD4+CCR4+ T-cells: possible role in atopic dermatitis. J Invest Dermatol 126:1043-51
95. Raap U, Werfel T, Goltz C, Deneka N, Langer K, Bruder M et al. (2006) Circulating levels of brain-derived neurotrophic factor correlate with disease severity in the intrinsic type of atopic dermatitis. Allergy 61:1416-8
96. Raap U, Wichmann K, Bruder M, Ständer S, Wedi B, Kapp A et al. (2008) Correlation of IL-31 serum levels with severity of atopic dermatitis. J Allergy Clin Immunol 122:421-3
97. Reefer AJ, Satinover SM, Wilson BB, Woodfolk JA (2007) The relevance of microbial allergens to the IgE antibody repertoire in atopic and nonatopic eczema. J Allergy Clin Immunol 120:156-63
98. Reekers R, Beyer K, Niggemann B, Wahn U, Freihorst J, Kapp A et al. (1996) The role of circulating food antigen-specific lymphocytes in food allergic children with atopic dermatitis. Br J Dermatol 135:935-41
99. Reekers R, Busche M, Wittmann M, Kapp A, Werfel T (1999) Birch pollen-related foods trigger atopic dermatitis in patients with specific cutaneous T-cell responses to birch pollen antigens. J Allergy Clin Immunol 104:466-72
100. Reich K, Hugo S, Middel P, Blaschke V, Heine A, Gutgesell C et al. (2002) Evidence for a role of Langerhans cell-derived IL-16 in atopic dermatitis. J Allergy Clin Immunol 109:681-7
101. Sager N, Feldmann A, Schilling G, Kreitsch P, Neumann C (1992) House dust mite-specific T-cells in the skin of subjects with atopic dermatitis: frequency and lymphokine profile in the allergen patch test. J Allergy Clin Immunol 89:801-10
102. Salt BH, Boguniewicz M, Leung DY (2007) Severe refractory atopic dermatitis in adults is highly atopic. J Allergy Clin Immunol 119:508-9 Sampson HA (2001) Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol 107:891-6
103. Santamaria Babi LF, Picker LJ, Perez Soler MT, Drzimalla K, Flohr P, Blaser K et al. (1995) Circulating allergen-reactive T-cells from patients with atopic dermatitis and allergic contact dermatitis express the skinselective homing receptor, the cutaneous lymphocyte-associated antigen. J Exp Med 181:1935-40
104. Scalabrin DM, Bavbek S, Perzanowski MS, Wilson BB, Platts-Mills TA, 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 104:1273-9
105. Scheynius A, Johansson C, Buentke E, Zargari A, Linder MT (2002) Atopic eczema/dermatitis syndrome and Malassezia. Int Arch Allergy Immunol 127:161-9
106. Schmid-Grendelmeier P, Fluckiger S, Disch R, Trautmann A, Wuthrich B, Blaser K et al. (2005) IgE-mediated and T-cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis. J Allergy Clin Immunol 115:1068-75
107. Schmid-Grendelmeier P, Scheynius A, Crameri R (2006) The role of sensitization to Malassezia sympodialis in atopic eczema. Chem Immunol Allergy 91:98-109
108. Schmid-Ott G, Jaeger B, Adamek C, Koch H, Lamprecht F, Kapp A et al. (2001a) Levels of circulating CD8(+) T-lymphocytes, natural killer cells, and eosinophils increase upon acute psychosocial stress in patients with atopic dermatitis. J Allergy Clin Immunol 107:171-7
109. Schmid-Ott G, Jaeger B, Meyer S, Stephan E, Kapp A, Werfel T (2001b) Different expression of cytokine and membrane molecules by circulating lymphocytes on acute mental stress in patients with atopic dermatitis in comparison with healthy controls. J Allergy Clin Immunol 108:455-62
110. Schnopp C, Rad R, Weidinger A, Weidinger S, Ring J, Eberlein B et al. (2007) Fox-P3- positive regulatory T-cells are present in the skin of generalized atopic eczema patients and are not particularly affected by mediumdose UVA1 therapy. Photodermatol Photoimmunol Photomed 23:81-5
111. Selander C, Zargari A, Mollby R, Rasool O, Scheynius A (2006) Higher pH level, corresponding to that on the skin of patients with atopic eczema, stimulates the release of Malassezia sympodialis allergens. Allergy 61:1002-8
112. Seneviratne SL, Jones L, King AS, Black A, Powell S, McMichael AJ et al. (2002) Allergenspecific CD8(+) T cells and atopic disease. J Clin Invest 110:1283-91
113. Shimizu M, Matsuda A, Yanagisawa K, Hirota T, Akahoshi M, Inomata N et al. (2005) Functional SNPs in the distal promoter of the ST2 gene are associated with atopic dermatitis. Hum Mol Genet 14:2919-27
114. Simon D, Braathen LR, Simon HU (2004) Eosinophils and atopic dermatitis. Allergy 59:561-70 Skov L, Olsen JV, Giorno R, Schlievert PM, Baadsgaard O, Leung DY (2000) Application of Staphylococcal enterotoxin B on normal and atopic skin induces up-regulation of T-cells by a superantigen-mediated mechanism. J Allergy Clin Immunol 105: 820-6
115. Sonkoly E, Muller A, Lauerma AI, Pivarcsi A, Soto H, Kemeny L et al. (2006) IL-31: a new link between T-cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol 117:411-7
116. Soumelis V, Liu YJ (2004) Human thymic stromal lymphopoietin: a novel epithelial cell-derived cytokine and a potential key player in the induction of allergic inflammation. Springer Semin Immunopathol 25:325-33
117. Spergel JM, Mizoguchi E, Oettgen H, Bhan AK, Geha RS (1999) Roles of TH-1 and TH-2 cytokines in a murine model of allergic dermatitis. J Clin Invest 103:1103-11
118. Steinhoff M, Steinhoff A, Homey B, Luger TA, Schneider SW (2006) Role of vasculature in atopic dermatitis. J Allergy Clin Immunol 118:190-7
119. Strange P, Skov L, Lisby S, Nielsen PL, Baadsgaard O (1996) Staphylococcal enterotoxin B applied on intact normal and intact atopic skin induces dermatitis. Arch Dermatol 132:27-33
120. Sugiura K, Muro Y, Nishizawa Y, Okamoto M, Shinohara T, Tomita Y et al. (2007) LEDGF/ DFS70, a major autoantigen of atopic dermatitis, is a component of keratohyalin granules. J Invest Dermatol 127:75-80
121. Szepietowski JC, McKenzie RC, Keohane SG, Aldridge RD, Hunter JA (1997) Atopic and non-atopic individuals react to nickel challenge in a similar way. A study of the cytokine profile in nickel-induced contact dermatitis. Br J Dermatol 137: 195-200
122. Takaoka A, Arai I, Sugimoto M, Honma Y, Futaki N, Nakamura A et al. (2006) Involvement of IL-31 on scratching behavior in NC/Nga mice with atopic-like dermatitis. Exp Dermatol 15:161-7
123. Tan BB, Weald D, Strickland I, Friedmann PS (1996) Double-blind controlled trial of effect of housedust-mite allergen avoidance on atopic dermatitis. Lancet 347:15-8
124. Thepen T, Langeveld-Wildschut EG, Bihari IC, van Wichen DF, Van Reijsen FC, Mudde GC et al. (1996) Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial TH-2 response to a TH- 1 response in situ: an immunocytochemical study. J Allergy Clin Immunol 97:828-37
125. Toda M, Leung DY, Molet S, Boguniewicz M, Taha R, Christodoulopoulos P et al. (2003) Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions. J Allergy Clin Immunol 111:875-81
126. Torgerson TR, Ochs HD (2007) Immune dysregulation, polyendocrinopathy, enteropathy, Xlinked: forkhead box protein 3 mutations and lack of regulatory T-cells. J Allergy Clin Immunol 120:744-50
127. Trautmann A, Akdis M, Kleemann D, Altznauer F, Simon HU, Graeve T et al. (2000) T-cellmediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J Clin Invest 106:25-35
128. Trautmann A, Altznauer F, Akdis M, Simon HU, Disch R, Brocker EB et al. (2001) The differential fate of cadherins during T-cellinduced keratinocyte apoptosis leads to spongiosis in eczematous dermatitis. J Invest Dermatol 117:927-34
129. Turjanmaa K, Darsow U, Niggemann B, Rance F, Vanto T, Werfel T (2006) EAACI/GA2LEN position paper: present status of the atopy patch test. Allergy 61:1377-84
130. Valenta R, Mittermann I, Werfel T, Garn H, Renz H (2009) Linking allergy to autoimmune disease. Trends Immunol 30:109-16
131. van Beelen AJ, Teunissen MB, Kapsenberg ML, de Jong EC (2007) Interleukin-17 in inflammatory skin disorders. Curr Opin Allergy Clin Immunol 7:374-81
132. Van Reijsen FC, Bruijnzeel-Koomen CA, Kalthoff FS, Maggi E, Romagnani S, Westland JK et al. (1992) Skin-derived aeroallergen-specific Tcell clones of Th-2 phenotype in patients with atopic dermatitis. J Allergy Clin Immunol 90:184-93
133. Van Reijsen FC, Felius A, Wauters EA, Bruijnzeel- Koomen CA, 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. 101:207-9
134. Verhagen J, Akdis M, Traidl-Hoffmann C, Schmid- Grendelmeier P, Hijnen D, Knol EF et al. (2006) Absence of T-regulatory cell expression and function in atopic dermatitis skin. J Allergy Clin Immunol 117:176-83
135. Vigo PG, Girgis KR, Pfuetze BL, Critchlow ME, Fisher J, Hussain I (2006) Efficacy of anti-IgE therapy in patients with atopic dermatitis. J Am Acad Dermatol 55:168-70
136. Wedi B, Raap U, Kapp A (1999) Significant delay of apoptosis and Fas resistance in eosinophils of subjects with intrinsic and extrinsic type of atopic dermatitis. Int Arch Allergy Immunol 118:234-5
137. Wedi B, Raap U, Lewrick H, Kapp A (1998) IL-4- induced apoptosis in peripheral blood eosinophils. J Allergy Clin Immunol 102:1013-20
138. Werfel T, Ahlers G, Schmidt P, Boeker M, Kapp A, Neumann C (1997a) Milk-responsive atopic dermatitis is associated with a casein-specific lymphocyte response in adolescent and adult patients. J Allergy Clin Immunol 99:124-33
139. Werfel T, Breuer K (2004) Role of food allergy in atopic dermatitis. Curr Opin Allergy Clin Immunol 4:379-85
140. Werfel T, Breuer K, Rueff F, Przybilla B, Worm M, Grewe M et al. (2006) Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study. Allergy 61:202-5
141. Werfel T, Hentschel M, Kapp A, Renz H (1997b) Dichotomy of blood- and skin-derived IL-4-producing allergen-specific T-cells and restricted V beta repertoire in nickelmediated contact dermatitis. J Immunol 158:2500-5
142. Werfel T, Kapp A (1998) Environmental and other major provocation factors in atopic dermatitis. Allergy 53:731-9
143. Werfel T, Kapp A (1999) What do we know about the etiopathology of the intrinsic type of atopic dermatitis? Curr Probl Dermatol 28:29-36
144. Werfel T, Morita A, Grewe M, Renz H, Wahn U, Krutmann J et al. (1996) Allergen specificity of skin-infiltrating T-cells is not restricted to a type-2 cytokine pattern in chronic skin lesions of atopic dermatitis. J Invest Dermatol 107:871-6
145. Williams H, Flohr C (2006) How epidemiology has challenged 3 prevailing concepts about atopic dermatitis. J Allergy Clin Immunol 118:209-13
146. Wittmann M, Alter M, Stunkel T, Kapp A, Werfel T (2004) Cell-to-cell contact between activated CD4+ T-lymphocytes and unprimed monocytes interferes with a TH-1 response. J Allergy Clin Immunol 114:965-73
147. Wittmann M, Kienlin P, Mommert S, Kapp A, Werfel T (2002) Suppression of IL-12 production by soluble CD40 ligand: evidence for involvement of the p44/42 mitogenactivated protein kinase pathway. J Immunol 168:3793-800
148. Wittmann M, Purwar R, Hartmann C, Gutzmer R, Werfel T (2005) Human keratinocytes respond to interleukin-18: implication for the course of chronic inflammatory skin diseases. J Invest Dermatol 124:1225-33
149. Wittmann M, Werfel T (2006) Interaction of keratinocytes with infiltrating lymphocytes in allergic eczematous skin diseases. Curr Opin Allergy Clin Immunol 6:329-34
150. Wollenberg A, Wagner M, Gunther S, Towarowski A, Tuma E, Moderer M et al. (2002) Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. J Invest Dermatol 119:1096-102
151. Wu K, Higashi N, Hansen ER, Lund M, Bang K, Thestrup-Pedersen K (2000) Telomerase activity is increased and telomere length shortened in T-cells from blood of patients with atopic dermatitis and psoriasis. J Immunol 165:4742-7
152. Zachary CB, Allen MH, MacDonald DM (1985) In situ quantification of T-lymphocyte subsets and Langerhans cells in the inflammatory infiltrate of atopic eczema. Br J Dermatol 112:149-56