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Immunologie des allergischen Kontaktekzems

Immunology of allergic contact dermatitis

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Zusammenfassung

Ekzeme zählen zu den häufigsten Krankheitsbildern in der dermatologischen Praxis. Im dermatologischen Sprachgebrauch umfasst der Begriff Ekzem (grch. ekzema = Aufgegangenes) eine Gruppe akuter und chronischer nichtinfektiöser Entzündungsreaktionen der Haut. Der relativen Gleichartigkeit, mit der sich die Symptomatik der ekzematösen Entzündungsreaktion klinisch und histologisch manifestiert, stehen jedoch grundlegende Unterschiede in der Pathogenese gegenüber. Beim Kontaktekzem werden prinzipiell 2 Hauptformen unterschieden: die irritative und die allergische Kontaktdermatitis. Bei der irritativen Kontaktdermatitis handelt es sich um eine primär nichtimmunologische Entzündungsreaktion der Haut auf verschiedenartige chemische und physikalische Reize. Davon grundsätzlich abzugrenzen ist die allergische Kontaktdermatitis, eine spezifische, zellvermittelte Immunreaktion, die in der Regel eine vorangegangene Sensibilisierung gegenüber einem Allergen voraussetzt. Die Kenntnis des komplexen Zusammenspiels von Immunzellen, Entzündungsmediatoren und Adhäsionsmolekülen in der Pathogenese bildet die Grundlage für ein besseres funktionelles Verständnis des allergischen Kontaktekzems und ist wesentliche Voraussetzung für die Entwicklung neuer therapeutischer Strategien.

Abstract

Eczema is one of the most common skin diseases in dermatological practice. The broad medical definition of eczema includes any acute but non-infectious inflammatory reaction of the skin. The relative homogeneity of both the clinical and histological manifestations of eczema is in stark contrast to the profound pathogenetic differences of its various forms. The group of contact dermatitis can be divided into two main categories: irritant and allergic. Irritant contact dermatitis is due to a principally non- immunological inflammatory reaction of the skin to various physical or chemical irritants. In sharp contrast, allergic contact dermatitis is an antigen-specific cellular immune response of the skin, which in general requires prior antigen-recognition and priming of immune cells. A comprehensive understanding of the complex interactions between immune cells, inflammatory mediators and adhesion molecules in the underlying pathogenesis of allergic contact dermatitis is key for a better functional understanding and the development of new therapeutic strategies.

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Literatur

  1. Akiba H, Kehren J, Ducluzeau M et al (2002) Skin inflammation during contact hypersensitivity is mediated by early recruitment of CD8+ T cytotoxic 1 cells inducing keratinocyte apoptosis. J Immunol 168:3079–3087

    PubMed  CAS  Google Scholar 

  2. Arrighi J, Rebsamen M, Rousset F et al (2001) A critical role for p38 mitogen-activated protein kinase in the maturation of human blood-derived dendritic cells induced by lipopolysaccharide, TNF-alpha and contact sensitizers. J Immunol 166:3837–3845

    PubMed  CAS  Google Scholar 

  3. Barker J, Mitra R, Griffiths C et al (1991) Keratinocytes as initiators of inflammation. Lancet 337:211–214

    Article  PubMed  CAS  Google Scholar 

  4. Becker D, Valk E, Zahn S et al (2003) Coupling of contact sensitizers to thiol groups is a key event for the activation of monocytes and monocyte-derived dendritic cells. J Invest Dermatol 120:233–238

    Article  PubMed  CAS  Google Scholar 

  5. Berg E, Yoshino T, Rott L et al (1991) The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1. J Exp Med 174:1461–1466

    Article  PubMed  CAS  Google Scholar 

  6. Bonecchi R, Bianchi G, Bordignon P et al (1998) Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 187:129–134

    Article  PubMed  CAS  Google Scholar 

  7. Bour H, Peyron E, Gaucherand M et al (1995) Major histocompatibility complex class I-restricted CD8+ T cells and class II-restricted CD4+ T cells, respectively, mediate and regulate contact sensitivity to dinitrofluorobenzene. Eur J Immunol 25:3006–3010

    Article  PubMed  CAS  Google Scholar 

  8. Brand P, Plochmann S, Valk E et al (2002) Activation and translocation of p38 mitogen-activated protein kinase after stimulation of monocytes with contact sensitizers. J Invest Dermatol 119:99–106

    Article  PubMed  CAS  Google Scholar 

  9. Cavani A, Nasorri F, Prezzi C et al (2000) Human CD4+ T lymphocytes with remarkable regulatory functions on dendritic cells and nickel-specific Th1 immune responses. J Invest Dermatol 114:295–302

    Article  PubMed  CAS  Google Scholar 

  10. Dufour J, Dziejman M, Liu M et al (2002) IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol 168:3195–3204

    PubMed  CAS  Google Scholar 

  11. Engeman T, Gorbachev A, Gladue R et al (2000) Inhibition of functional T cell priming and contact hypersensitivity responses by treatment with anti-secondary lymphoid chemokine antibody during hapten sensitization. J Immunol 164:5207–5214

    PubMed  CAS  Google Scholar 

  12. Enk A, Katz S (1992) Early molecular events in the induction phase of contact sensitivity. Proc Natl Acad Sci USA 89:1398–1402

    Article  PubMed  CAS  Google Scholar 

  13. Enk A, Katz S (1992) Identification and induction of keratinocyte-derived IL-10. J Immunol 149:92–95

    PubMed  CAS  Google Scholar 

  14. Ferguson T, Dube P, Griffith T (1994) Regulation of contact hypersensitivity by interleukin 10. J Exp Med 179:1597–1604

    Article  PubMed  CAS  Google Scholar 

  15. Ghoreishi M, Dutz J (2006) Tolerance induction by transcutaneous immunization through ultraviolet-irradiated skin is transferable through CD4+CD25+ T regulatory cells and is dependent on host-derived IL-10. J Immunol 176:2635–2644

    PubMed  CAS  Google Scholar 

  16. Gocinski B, Tigelaar R (1990) Roles of CD4+ and CD8+ T cells in murine contact sensitivity revealed by in vivo monoclonal antibody depletion. J Immunol 144:4121–4128

    PubMed  CAS  Google Scholar 

  17. Gorbachev A, Fairchild R (2001) Induction and regulation of T-cell priming for contact hypersensitivity. Crit Rev Immunol 21:451–472

    PubMed  CAS  Google Scholar 

  18. Gorbachev A, Fairchild R (2001) Regulatory role of CD4+ T cells during the development of contact hypersensitivity responses. Immunol Res 24:69–77

    Article  PubMed  CAS  Google Scholar 

  19. Grabbe S, Schwarz T (1998) Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity. Immunol Today 19:37–44

    Article  PubMed  CAS  Google Scholar 

  20. Grabbe S, Steinert M, Mahnke K et al (1996) Dissection of antigenic and irritative effects of epicutaneously applied haptens in mice. Evidence that not the antigenic component but nonspecific proinflammatory effects of haptens determine the concentration-dependent elicitation of allergic contact dermatitis. J Clin Invest 98:1158–1164

    Article  PubMed  CAS  Google Scholar 

  21. Groves R, Allen M, Ross E et al (1995) Tumour necrosis factor alpha is pro-inflammatory in normal human skin and modulates cutaneous adhesion molecule expression. Br J Dermatol 132:345–352

    Article  PubMed  CAS  Google Scholar 

  22. Gunn M, Kyuwa S, Tam C et al (1999) Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization. J Exp Med 189:451–460

    Article  PubMed  CAS  Google Scholar 

  23. Homey B, Alenius H, Muller A et al (2002) CCL27-CCR10 interactions regulate T cell-mediated skin inflammation. Nat Med 8:157–165

    Article  PubMed  CAS  Google Scholar 

  24. Kuhn U, Brand P, Willemsen J et al (1998) Induction of tyrosine phosphorylation in human MHC class II-positive antigen-presenting cells by stimulation with contact sensitizers. J Immunol 160:667–673

    PubMed  CAS  Google Scholar 

  25. Kupper T, Groves R (1995) The interleukin-1 axis and cutaneous inflammation. J Invest Dermatol 105:62S–66S

    Article  PubMed  CAS  Google Scholar 

  26. Landsteiner K, Jl J (1936) Studies on the sensitization of animals with simple chemicals. J Exp Med:625–639

    Article  Google Scholar 

  27. Lowin B, Hahne M, Mattmann C et al (1994) Cytolytic T-cell cytotoxicity is mediated through perforin and fas lytic pathways. Nature 370:650–652

    Article  PubMed  CAS  Google Scholar 

  28. Martin S, Dudda J, Bachtanian E et al (2008) Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivity. J Exp Med 205:2151–2162

    Article  PubMed  CAS  Google Scholar 

  29. Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10:417–426

    Article  PubMed  CAS  Google Scholar 

  30. Maurer M, Seidel-Guyenot W, Metz M et al (2003) Critical role of IL-10 in the induction of low zone tolerance to contact allergens. J Clin Invest 112:432–439

    PubMed  CAS  Google Scholar 

  31. Mckenzie R, Sauder D (1990) The role of keratinocyte cytokines in inflammation and immunity. J Invest Dermatol 95:105S–107S

    Article  PubMed  CAS  Google Scholar 

  32. Nakae S, Komiyama Y, Nambu A et al (2002) Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity 17:375–387

    Article  PubMed  CAS  Google Scholar 

  33. Neisius U, Brand P, Plochmann S et al (1999) Detection of increased tyrosine phosphorylation in murine Langerhans cells after stimulation with contact sensitizers. Arch Dermatol Res 291:22–27

    Article  PubMed  CAS  Google Scholar 

  34. Ortmann B, Martin S, Bonin A von et al (1992) Synthetic peptides anchor T cell-specific TNP epitopes to MHC antigens. J Immunol 148:1445–1450

    PubMed  CAS  Google Scholar 

  35. Paradis T, Cole S, Nelson R et al (2008) Essential role of CCR6 in directing activated T cells to the skin during contact hypersensitivity. J Invest Dermatol 128:628–633

    PubMed  CAS  Google Scholar 

  36. Paulnock D (1992) Macrophage activation by T cells. Curr Opin Immunol 4:344–349

    Article  PubMed  CAS  Google Scholar 

  37. Reiss Y, Proudfoot A, Power C et al (2001) CC chemokine receptor (CCR)4 and the CCR10 ligand cutaneous T cell-attracting chemokine (CTACK) in lymphocyte trafficking to inflamed skin. J Exp Med 194:1541–1547

    Article  PubMed  CAS  Google Scholar 

  38. Saeki H, Moore A, Brown M et al (1999) Cutting edge: secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes. J Immunol 162:2472–2475

    PubMed  CAS  Google Scholar 

  39. Saint-Mezard P, Berard F, Dubois B et al (2004) The role of CD4+ and CD8+ T cells in contact hypersensitivity and allergic contact dermatitis. Eur J Dermatol 14:131–138

    PubMed  Google Scholar 

  40. Saint-Mezard P, Krasteva M, Chavagnac C et al (2003) Afferent and efferent phases of allergic contact dermatitis (ACD) can be induced after a single skin contact with haptens: evidence using a mouse model of primary ACD. J Invest Dermatol 120:641–647

    Article  PubMed  CAS  Google Scholar 

  41. Sallusto F, Lenig D, Forster R et al (1999) Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401:708–712

    Article  PubMed  CAS  Google Scholar 

  42. Sallusto F, Palermo B, Lenig D et al (1999) Distinct patterns and kinetics of chemokine production regulate dendritic cell function. Eur J Immunol 29:1617–1625

    Article  PubMed  CAS  Google Scholar 

  43. Sauder D (1990) The role of epidermal cytokines in inflammatory skin diseases. J Invest Dermatol 95:27S–28S

    Article  Google Scholar 

  44. Schutyser E, Struyf S, Damme J Van (2003) The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth Factor Rev 14:409–426

    Article  PubMed  CAS  Google Scholar 

  45. Schwarz A, Grabbe S, Riemann H et al (1994) In vivo effects of interleukin-10 on contact hypersensitivity and delayed-type hypersensitivity reactions. J Invest Dermatol 103:211–216

    Article  PubMed  CAS  Google Scholar 

  46. Sebastiani S, Allavena P, Albanesi C et al (2001) Chemokine receptor expression and function in CD4+ T lymphocytes with regulatory activity. J Immunol 166:996–1002

    PubMed  CAS  Google Scholar 

  47. Shornick L, De Togni P, Mariathasan S et al (1996) Mice deficient in IL-1beta manifest impaired contact hypersensitivity to trinitrochlorobenzone. J Exp Med 183:1427–1436

    Article  PubMed  CAS  Google Scholar 

  48. Steinbrink K, Kolde G, Sorg C et al (1996) Induction of low zone tolerance to contact allergens in mice does not require functional Langerhans cells. J Invest Dermatol 107:243–247

    Article  PubMed  CAS  Google Scholar 

  49. Steinbrink K, Sorg C, Macher E (1996) Low zone tolerance to contact allergens in mice: a functional role for CD8+ T helper type 2 cells. J Exp Med 183:759–768

    Article  PubMed  CAS  Google Scholar 

  50. Sullivan S, Bergstresser P, Streilein J (1990) Analysis of dose response of trinitrochlorobenzene contact hypersensitivity induction in mice: pretreatment with cyclophosphamide reveals an optimal sensitizing dose. J Invest Dermatol 94:711–716

    Article  PubMed  CAS  Google Scholar 

  51. Sunday M, Benacerraf B, Dorf M (1981) Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. VIII. Suppressor cell pathways in cutaneous sensitivity responses. J Exp Med 153:811–822

    Article  PubMed  CAS  Google Scholar 

  52. Trautmann A, Akdis M, Kleemann D et al (2000) T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J Clin Invest 106:25–35

    Article  PubMed  CAS  Google Scholar 

  53. Vigan M, Girardin P, Adessi B et al (1997) Late reading of patch tests. Eur J Dermatol:574–576

    Google Scholar 

  54. Wang B, Feliciani C, Howell B et al (2002) Contribution of Langerhans cell-derived IL-18 to contact hypersensitivity. J Immunol 168:3303–3308

    PubMed  CAS  Google Scholar 

  55. Watanabe H, Gaide O, Petrilli V et al (2007) Activation of the IL-1beta-processing inflammasome is involved in contact hypersensitivity. J Invest Dermatol 127:1956–1963

    Article  PubMed  CAS  Google Scholar 

  56. Watanabe H, Gehrke S, Contassot E et al (2008) Danger signaling through the inflammasome acts as a master switch between tolerance and sensitization. J Immunol 180:5826–5832

    PubMed  CAS  Google Scholar 

  57. Watanabe H, Unger M, Tuvel B et al (2002) Contact hypersensitivity: the mechanism of immune responses and T cell balance. J Interferon Cytokine Res 22:407–412

    Article  PubMed  CAS  Google Scholar 

  58. Xu H, Diiulio N, Fairchild R (1996) T cell populations primed by hapten sensitization in contact sensitivity are distinguished by polarized patterns of cytokine production: interferon gamma-producing (Tc1) effector CD8+ T cells and interleukin (Il) 4/Il-10-producing (Th2) negative regulatory CD4+ T cells. J Exp Med 183:1001–1012

    Article  PubMed  CAS  Google Scholar 

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  1. Universitäts-Hautklinik, Voßstraße 11, 69115, Heidelberg, Deutschland

    A.S. Lonsdorf & A.H. Enk

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Lonsdorf, A., Enk, A. Immunologie des allergischen Kontaktekzems. Hautarzt 60, 32–41 (2009). https://doi.org/10.1007/s00105-008-1642-8

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