Pathophysiologie der Psoriasis

 

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Zusammenfassung

Erkenntnisse zur (Immun-)Pathogenese der Psoriasis haben einerseits kürzlich zur Einführung mehrerer Pathogenese-orientierter Therapeutika geführt; andererseits haben diese neuen Therapien auch der Psoriasisforschung einen beispiellosen Aufschwung beschert. Insbesondere die Rolle entzündlicher Mediatoren wie Zytokine und Chemokine, aber auch die Funktion von Adhäsionsmolekülen bei der Rekrutierung von Immunzellen wurden intensiv beforscht. Diese Facetten müssen jedoch, und das wird gerade durch neueste Arbeiten verdeutlicht, durch weitere Bausteine eines komplexen Mosaikes, welches auch epidermale und neuronale Faktoren beinhaltet, ergänzt werden. Die komplexen Zusammenhänge der Pathophysiologie der Psoriasis werden in dieser Übersicht diskutiert.

Abstract

On the one hand, new insights into the (immuno-)pathogenesis of psoriasis have recently resulted in the approval of several pathogenesis-oriented novel therapeutics. These new therapies, on the other hand, have greatly stimulated research into the pathogenesis of psoriasis. In particular, pro-inflammatory mediators such as cytokines and chemokines as well as adhesion molecules involved in recruitment of immune cells into the skin have been in the focus of psoriasis research. However, new results indicate that the pathogenic mosaic of psoriasis has to be complemented by other important factors, such as epithelial or neurological dysregulations. This review discusses aspects of the complex pathophysiology of psoriasis.

Literatur

• 1 Schön M P, Boehncke W H. Psoriasis.  N Engl J Med. 2005;  352 1899-1912
  CrossrefPubMedGoogle Scholar
• 2 Gottlieb A B. Psoriasis: emerging therapeutic strategies.  Nat Rev Drug Discov. 2005;  4 19-34
  PubMedGoogle Scholar
• 3 Schön M P. Advances in psoriasis therapy.  Lancet. 2005;  366 1333-1335
  CrossrefPubMedGoogle Scholar
• 4 Nickoloff B J. Keratinocytes regain momentum as instigators of cutaneous inflammation.  Trend Mol Med. 2006;  12 102-106
  PubMedGoogle Scholar
• 5 Christophers E. The immunopathology of psoriasis.  Int Arch Allergy Immunol. 1996;  110 199-206
  PubMedGoogle Scholar
• 6 Mueller W, Herrmann B. Cyclosporin A for psoriasis.  N Engl J Med. 1979;  301 555
  PubMedGoogle Scholar
• 7 Gottlieb J L, Gilleaudeau P, Johnson R, Estes L, Woodworth T G, Gottlieb A B, Krueger J G. Response of psoriasis to a lymphocyte-selective toxin (DAB389 IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis.  Nature Med. 1995;  1 442-447
  PubMedGoogle Scholar
• 8 Ellis C N, Krueger G G, Group A CS. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes.  N Engl J Med. 2001;  345 248-255
  CrossrefPubMedGoogle Scholar
• 9 Kupper T S. Immunologic targets in psoriasis.  New Engl J Med. 2003;  349 1987-1990
  CrossrefPubMedGoogle Scholar
• 10 Lebwohl M, Tyring S K, Hamilton T K, Toth D, Glazer S, Tawfik N H, Walicke P, Dummer W, Wang X, Garovoy M R, Pariser D. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis.  New Engl J Med. 2003;  349 2004-2013
  CrossrefPubMedGoogle Scholar
• 11 Nicolas J F, Chamchick N, Thivolet J, Wijdenes J, Morel P, Revillard J P. CD4 antibody treatment of severe psoriasis.  Lancet. 1991;  338 321
  PubMedGoogle Scholar
• 12 Prinz J, Braun-Falco O, Meurer M, Daddona P, Reiter C, Rieber P, Riethmuller G. Chimaeric CD4 monoclonal antibody in treatment of generalized pustular psoriasis.  Lancet. 1991;  338 320-321
  PubMedGoogle Scholar
• 13 Tomfohrde J, Silverman A, Barnes R, Fernandez-Vina M A, Young M, Lory D, Morris L, Wuepper K D, Stastny P, Menter A, Bowcock A. Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q.  Science. 1994;  264 1141-1145
  PubMedGoogle Scholar
• 14 Eedy D J, Burrows D, Bridges J M, Jones F GC. Clearance of severe psoriasis after allogeneic bone marrow transplantation.  Br Med J. 1990;  300 908
  PubMedGoogle Scholar
• 15 Gardembas-Pain M, Ifrah N, Foussard C, Boasson M, Saint Andre J P, Verret J L. Psoriasis after allogeneic bone marrow transplantation.  Arch Dermatol. 1990;  126 1523
  CrossrefPubMedGoogle Scholar
• 16 Christophers E. Psoriasis - Epidemiology and clinical spectrum.  Clin Exp Dermatol. 2001;  26 314-320
  CrossrefPubMedGoogle Scholar
• 17 Bour H, Puisieux I, Kouritsky P, Favrot M, Musette P, Nicolas J F. T-cell repertoire analysis in chronic plaque psoriasis suggests an antigen-specific immune response.  Hum Immunol. 1999;  60 665-676
  CrossrefPubMedGoogle Scholar
• 18 Lin W J, Norris D A, Achziger M, Kotzin B L, Tomkinson B. Oligoclonal expansion of intraepidermal T cells in psoriasis skin lesions.  J Invest Dermatol. 2001;  117 1546-1553
  CrossrefPubMedGoogle Scholar
• 19 Prinz J C, Vollmer S, Boehncke W H, Menssen A, Laisney I, Trommler P. Selection of conserved TCR VDJ rearrangements in chronic psoriatic plaques indicates a common antigen in psoriasis vulgaris.  Eur J Immunol. 1999;  29 3360-3368
  CrossrefPubMedGoogle Scholar
• 20 Boehncke W-H. Psoriasis and bacterial superantigens - formal or causal relation?.  Trends Microbiol.. 1996;  4 485-489
  CrossrefPubMedGoogle Scholar
• 21 Vekony M A, Holder J E, Lee A J, Horrocks C, Eperon I C, Camp R D. Selective amplifications of T-cell receptor variable region species is demonstrable but not essential in early lesions of psoriasis vulgaris: analysis by anchored polymerase chain reaction and hypervariable region size spectratyping.  J Invest Dermatol. 1997;  109 5-13
  CrossrefPubMedGoogle Scholar
• 22 Weisenseel P, Laumbacher B, Besgen P, Ludolph-Hauser D, Herzinger T, Röcken M, Wank R, Prinz J C. Streptococcal infection distinguishes different types of psoriasis.  J Med Genet. 2002;  39 767-768
  CrossrefPubMedGoogle Scholar
• 23 Boehncke W-H, Dressel D, Zollner T M, Kaufmann R. Pulling the trigger on psoriasis.  Nature. 1996;  379 777
  PubMedGoogle Scholar
• 24 Gudmundsdottir A S, Sigmundsdottir H, Sigurgeirsson B, Good M F, Valdimarsson H, Jonsdottir I. Is an epitope on keratin 17 a major target for autoreactive T lymphocytes in psoriasis?.  Clin Exp Immunol. 1999;  117 580-586
  CrossrefPubMedGoogle Scholar
• 25 Schön M P. Animal models of psoriasis - what can we learn from them?.  J Invest Dermatol. 1999;  112 405-410
  CrossrefPubMedGoogle Scholar
• 26 Wrone-Smith T, Nickoloff B J. Dermal injection of immunocytes induces psoriasis.  J Clin Invest. 1996;  98 1878-1887
  CrossrefPubMedGoogle Scholar
• 27 Boyman O, Hefti H P, Conrad C, Nickoloff B J, Suter M, Nestle F O. Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor alpha.  J Exp Med. 2004;  199 731-736
  CrossrefPubMedGoogle Scholar
• 28 Breban M, Fernandez-Sueiro J L, Richardson J A, Hadavand R R, Maika S D, Hammer R E, Taurog J D. T cells, but not thymic exposure to HLA-B27, are required for the inflammatory disease of HLA-B27 transgenic rats.  J Immunol. 1996;  156 794-803
  PubMedGoogle Scholar
• 29 Schön M P, Detmar M, Parker C M. Murine psoriasis-like disorder induced by naive CD4⁺ T-cells.  Nature Med. 1997;  3 183-188
  PubMedGoogle Scholar
• 30 Bos J D, de Rie M A, Teunissen M B, Piskin G. Psoriasis: dysregulation of innate immunity.  Br J Dermatol. 2005;  152 1098-1107
  CrossrefPubMedGoogle Scholar
• 31 von den Driesch P. Is psoriasis a T-cell disease? Viewpoint 3.  Exp Dermatol. 2000;  9 367-377
  PubMedGoogle Scholar
• 32 Schön M, Denzer D, Kubitza R C, Ruzicka T, Schön M P. Critical role of neutrophils for the generation of psoriasiform skin lesions in flaky skin mice.  J Invest Dermatol. 2000;  114 976-983
  CrossrefPubMedGoogle Scholar
• 33 Zhu K, Mrowietz U. Enhancement of antibacterial superoxide-anion generation in human monocytes by fumaric acid esters.  Arch Dermatol Res. 2005;  297 170-176
  CrossrefPubMedGoogle Scholar
• 34 Schaerli P, Britschgi M, Keller M, Steiner U C, Steinmann L S, Moser B, Pichler W J. Characterization of human T cells that regulate neutrophilic skin inflammation.  J Immunol. 2004;  173 2151-2158
  PubMedGoogle Scholar
• 35 Keller M, Spanou Z, Schaerli P, Britschgi M, Yawalkar N, Seitz M, Villiger P M, Pichler W J. T cell-regulated neutrophilic inflammation in autoinflammatory diseases.  J Immunol. 2005;  175 7678-7686
  PubMedGoogle Scholar
• 36 Nickoloff B J. The cytokine network of psoriasis.  Arch Dermatol. 1991;  127 871-884
  CrossrefPubMedGoogle Scholar
• 37 Schön M P, Ruzicka T. Psoriasis: The plot thickens.  Nat Immunol. 2001;  2 91
  CrossrefPubMedGoogle Scholar
• 38 Barker J NWN, Sarma V, Mitra R S, Dixit V M, Nickoloff B J. Marked synergism between tumor necrosis factor-alpha and interferon-gamma in regulation of keratinocyte-derived adhesion molecules and chemotactic factors.  J Clin Invest. 1990;  85 605-608
  PubMedGoogle Scholar
• 39 Murphy J E, Robert C, Kupper T S. Interleukin-1 and cutaneous inflammation: a crucial link between innate and acquired immunity.  J Invest Dermatol. 2000;  114 602-608
  CrossrefPubMedGoogle Scholar
• 40 Neuner P, Urbanski A, Trautinger F, Moller A, Kirnbauer R, Kapp A, Schopf E, Schwarz T, Luger T A. Increased IL-6 production by monocytes and keratinocytes in patients with psoriasis.  J Invest Dermatol. 1991;  97 27-33
  CrossrefPubMedGoogle Scholar
• 41 Leonardi C L, Powers J L, Matheson R T, Goffe B S, Zitnik R, Wang A, Gottlieb A B,. T.e.p.s. group . Etanercept as monotherapy in patients with psoriasis.  N Engl J Med. 2003;  349 2014-2022
  CrossrefPubMedGoogle Scholar
• 42 Reich K, Nestle F O, Papp K, Ortonne J P, Evans R, Guzzo C, Li S, Dooley L T, Griffiths C EM. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis.  Lancet. 2005;  366 1367-1374
  CrossrefPubMedGoogle Scholar
• 43 Kuroda K, Sapadin A, Shoji T, Fleischmajer R, Lebwohl M. Altered expression of angiopoietins and Tie2 endothelium receptor in psoriasis.  J Invest Dermatol. 2001;  116 713-720
  CrossrefPubMedGoogle Scholar
• 44 Detmar M, Brown L F, Claffey K P, Yeo K T, Kocher O, Jackman R W, Berse B, Dvorak H F. Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis.  J Exp Med. 1994;  180 1141-1146
  CrossrefPubMedGoogle Scholar
• 45 Michel G, Mirmohammadsadegh A, Olasz E, Jarzebska-Deussen B, Müschen A, Kemeny L, Abts H F, Ruzicka T. Demonstration and functional analysis of IL-10 receptors in human epidermal cells: decreased expression in psoriatic skin, down-modulation by IL-8, and up-regulation by an antipsoriatic glucocorticosteroid in normal cultured keratinocytes.  J Immunol. 1997;  159 6291-6297
  PubMedGoogle Scholar
• 46 Asadullah K, Sterry W, Stephanek K. IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach.  J Clin Invest. 1998;  101 783-794
  CrossrefPubMedGoogle Scholar
• 47 Ghoreschi K, Thomas P, Dugas M, Mailhammer R, van Eden W, van der Zee R, Biedermann T, Prinz J, Mack M, Mrowietz U, Christophers E, Schlöndorff D, Plewig G, Sander C A, Röcken M. Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease.  Nature Med. 2003;  9 40-46
  PubMedGoogle Scholar
• 48 Ghoreschi K, Röcken M. Immune deviation strategies in the therapy of psoriasis.  Curr Drug Targets Inflamm Allergy. 2004;  3 193-198
  CrossrefPubMedGoogle Scholar
• 49 Asadullah K, Volk H D, Sterry W. Novel immunotherapies for psoriasis.  Trends Immunol. 2002;  23 47-53
  CrossrefPubMedGoogle Scholar
• 50 Homey B. Chemokines and chemokine receptors as targets in the therapy of psoriasis.  Curr Drug Targets Inflamm Allerg. 2004;  3 169-174
  PubMedGoogle Scholar
• 51 Campbell J J, Haraldsen G, Pan J, Rottman J, Qin S, Ponath P, Andrew D P, Warnke R, Ruffing N, Kassam N, Wu L, Butcher E C. The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells.  Nature. 1999;  400 776-780
  PubMedGoogle Scholar
• 52 Homey B, Alenius H, Müller A, Soto H, Bowman E P, Yuan W, McEvoy L, Lauerma A I, Assmann T, Bünemann E, Lehto M, Wolff H, Yen D, Marxhausen H, To W, Sedgwick J, Ruzicka T, Lehmann P, Zlotnik A. CCL27-CCR10 interactions regulate T cell-mediated skin inflammation.  Nature Med. 2002;  8 157-165
  PubMedGoogle Scholar
• 53 Goebeler M, Toksoy A, Spandau U, Engelhardt E, Bröcker E-B, Gillitzer R. The C-X-C chemokine Mig is highly expressed in the papillae of psoriatic lesions.  J Pathol. 1998;  184 89-95
  PubMedGoogle Scholar
• 54 Liao F, Rabin R L, Yannelli J R, Koniaris L G, Vanguri P, Farber J M. Human Mig chemokine: biochemical and functional characterization.  J Exp Med. 1995;  182 1301-1314
  CrossrefPubMedGoogle Scholar
• 55 Raychaudhuri S P, Jiang W Y, Farber E M, Schall T J, Ruff M R, Pert C B. Upregulation of RANTES in psoriatic keratinocytes: a possible pathogenic mechanism for psoriasis.  Acta Derm Venereol. 1999;  79 9-11
  PubMedGoogle Scholar
• 56 Vestergaard C, Gesser B, Lohse N, Jensen S L, Sindet-Pedersen S, Thestrup-Pedersen K, Matsushima K, Larsen C G. Monocyte chemotactic and activating factor (MCAF/MCP-1) has an autoinductive effect in monocytes, a process regulated by IL-10.  J Dermatol Sci. 1997;  15 14-22
  CrossrefPubMedGoogle Scholar
• 57 Schröder J M, Gregory H, Young J, Christophers E. Neutrophil-activating proteins in psoriasis.  J Invest Dermatol. 1992;  98 241-247
  CrossrefPubMedGoogle Scholar
• 58 Schön M P, Zollner T M, Boehncke W H. The molecular basis of lymphocyte recruitment to the skin: Clues for pathogenesis and selective therapies of inflammatory disorders.  J Invest Dermatol. 2003;  121 951-962
  CrossrefPubMedGoogle Scholar
• 59 Dewing S B. Remission of psoriasis associated with cutaneous nerve section.  Arch Dermatol. 1971;  104 220-221
  CrossrefPubMedGoogle Scholar
• 60 Perlman H H. Remission of psoriasis vulgaris from the use of nerve-blocking agents.  Arch Dermatol. 1972;  105 128-129
  CrossrefPubMedGoogle Scholar
• 61 Scholzen T E, Luger T A. Neutral endopeptidase and angiotensin-converting enzyme - key enzymes terminating the action of neuroendocrine mediators.  Exp Dermatol. 2004;  13s 22s-26s
  PubMedGoogle Scholar
• 62 Raychaudhuri S P, Raychaudhuri S K. Role of NGF and neurogenic inflammation in the pathogenesis of psoriasis.  Prog Brain Res. 2004;  146 433-437
  PubMedGoogle Scholar
• 63 Steinhoff M, Ständer S, Seeliger S, Ansel J C, Schmelz M, Luger T A. Modern aspects of cutaneous neurogenic inflammation.  Arch Dermatol. 2003;  139 1479-1488
  CrossrefPubMedGoogle Scholar
• 64 Raychaudhuri S P, Sanyal M, Weltman H, Kundu-Raychaudhuri S. K252a, a high-affinity nerve growth factor receptor blocker, improves psoriasis: an in vivo study using the severe combined immunodeficient mouse-human skin model.  J Invest Dermatol. 2004;  122 812-819
  CrossrefPubMedGoogle Scholar
• 65 Robert C, Kupper T S. Inflammatory skin diseases, T cells, and immune surveillance.  N Engl J Med. 1999;  341 1817-1828
  CrossrefPubMedGoogle Scholar
• 66 Lebwohl M. Psoriasis.  Lancet. 2003;  361 1197-1204
  CrossrefPubMedGoogle Scholar
• 67 Papp K, Bissonnette R, Krueger J G, Carey W, Gratton D, Gulliver W P, Lui H, Lynde C W, Magee A, Minier D, Ouellet J P, Patel P, Shapiro J, Shear N H, Kramer S, Walicke P, Bauer R, Dedrick R L, Kim S S, White M, Garovoy M R. The treatment of moderate to severe psoriasis with a new anti-CD11a monoclonal antibody.  J Am Acad Dermatol. 2001;  45 665-674
  CrossrefPubMedGoogle Scholar
• 68 Butcher E C, Picker L J. Lymphocyte homing and homeostasis.  Science. 1996;  272 60-66
  CrossrefPubMedGoogle Scholar
• 69 Andrian U H von, Mackay C R. T-cell function and migration. Two sides of the same coin.  N Engl J Med. 2000;  343 1020-1034
  CrossrefPubMedGoogle Scholar
• 70 Ley K. Functions of selectins.  Results Probl Cell Differ. 2001;  33 177-200
  PubMedGoogle Scholar
• 71 Fuhlbrigge R C, Kieffer J D, Armerding D, Kupper T S. Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells.  Nature. 1997;  389 978-981
  CrossrefPubMedGoogle Scholar
• 72 Bhushan M, Bleiker T O, Ballsdon A E, Allen M H, Sopwith M, Robinson M K, Clarke C, Weller R P, Graham-Brown R A, Keefe M, Barker J N, Griffiths C E. Anti-E-selectin is ineffective in the treatment of psoriasis: a randomized trial.  Br J Dermatol. 2002;  146 824-831
  PubMedGoogle Scholar
• 73 Hardtke M, Friedrich M, Philipp S, Holzmann R, Mueller C, Soos N, Höflich C, Sabat R, Merk H, Sterry W, Mrowietz U. Anti-L-selectin therapy is not effective in psoriasis: a randomized trial (abstr.).  Arch Dermatol Res. 2005;  296 427
  PubMedGoogle Scholar
• 74 Boehncke W-H, Schön M P. Interfering with leukocyte rolling - a promising therapeutic approach in inflammatory skin disorders?.  Trends Pharmacol Sci. 2003;  24 49-52
  CrossrefPubMedGoogle Scholar
• 75 Friedrich M, Bock D, Philipp S, Ludwig N, Sabat R, Wolk K, Schroeter-Maas S, Aydt E, Kang S, Dam T N, Zahlten R, Sterry W, Wolff G. Pan-selectin antagonism improves psoriasis manifestation in mice and man.  Arch Dermatol Res. 2006;  297 345-351
  CrossrefPubMedGoogle Scholar
• 76 Schön M P, Drewniok C, Boehncke W H. Targeting selectin functions in the therapy of psoriasis.  Curr Drug Targets Inflamm Allerg. 2004;  3 163-168
  PubMedGoogle Scholar
• 77 Schön M P, Krahn T, Schön M, Rodriguez M-L, Antonicek H, Schultz J E, Ludwig R J, Zollner T M, Bischoff E, Bremm K-D, Schramm M, Henninger K, Kaufmann R, Gollnick H PM, Parker C M, Boehncke W-H. Efomycine M, a new specific inhibitor of selectin, impairs leukocyte adhesion and alleviates cutaneous inflammation.  Nature Med. 2002;  8 366-372
  PubMedGoogle Scholar
• 78 Ulbrich H, Eriksson E E, Lindbom L. Leukocyte and endothelial cell adhesion molecules as targets for therapeutic interventions in inflammatory disease.  Trends Pharmacol Sci. 2003;  24 640-647
  CrossrefPubMedGoogle Scholar
• 79 Hwang S T. Mechanisms of T cell homing to skin.  Adv Dermatol. 2001;  17 211-241
  PubMedGoogle Scholar
• 80 Ludwig R J, Zollner T M, Santoso S, Hardt K, Gille J, Baatz H, Johann P S, Pfeffer J, Radeke H H, Schön M P, Kaufmann R, Boehncke W H, Podda M. Junctional adhesion molecules (JAM)-B and -C contribute to leukocyte extravasation to the skin and mediate cutaneous inflammation.  J Invest Dermatol. 2005;  125 969-976
  PubMedGoogle Scholar
• 81 Nakada M T, Amin K, Christofidou-Solomidou M, O'Brien C D, Sun J, Gurubhagavatula I, Heavner G A, Taylor A H, Paddock C, Sun Q H, Zehnder J L, Newman P J, Albelda S M, DeLisser H M. Antibodies against the first Ig-like domain of human platelet endothelial cell adhesion molecule-1 (PECAM-1) that inhibit PECAM-1-dependent homophilic adhesion block in vivo neutrophil recruitment.  J Immunol. 2000;  164 452-462
  PubMedGoogle Scholar
• 82 Dustin M L, Singer K H, Springer T. Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and is mediated by intercellular adhesion molecule-1.  J Exp Med. 1988;  167 1323-1340
  CrossrefPubMedGoogle Scholar
• 83 Griffiths C EM, Voorhees J J, Nickoloff B J. Characterization of intercellular adhesion molecule-1 and HLA-DR expression in normal and inflamed skin: Modulation by recombinant gamma interferon and tumor necrosis factor.  J Am Acad Dermatol. 1989;  20 617-629
  PubMedGoogle Scholar
• 84 Sterry W, Mielke V, Konter U, Kellner I, Boehncke W-H. Role of β1 integrins in epidermotropism of malignant T cells.  Am J Pathol. 1992;  141 855-860
  PubMedGoogle Scholar
• 85 Cepek K L, Shaw S K, Parker C M, Russell G J, Morrow J S, Rimm D L, Brenner M B. Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the alphaEbeta7 integrin.  Nature. 1994;  372 190-193
  PubMedGoogle Scholar
• 86 Pauls K, Schön M, Kubitza R C, Homey B, Wiesenborn A, Lehmann P, Ruzicka T, Parker C M, Schön M P. Role of integrin αE(CD103)β7 for tissue-specific epidermal localization of CD8+ T lymphocytes.  J Invest Dermatol. 2001;  117 569-575
  CrossrefPubMedGoogle Scholar
• 87 Rottman J B, Smith T L, Ganley K G, Kikuchi T, Krueger J G. Potential role of the chemokine receptors CXCR3, CCR4, and the integrin aEb7 in the pathogenesis of psoriasis vulgaris.  Lab Invest. 2001;  81 335-347
  PubMedGoogle Scholar
• 88 Zenz R, Eferl R, Kenner L, Florin L, Hummerich L, Mehic D, Scheuch H, Angel P, Tschachler E, and Wagner EF. Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins.  Nature. 2005;  437 369-375
  CrossrefPubMedGoogle Scholar
• 89 Sano S, Chan K S, Carbajal S, Clifford J, Peavey M, Kiguchi K, Itami S, Nickoloff B J, DiGiovanni J. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model.  Nat Med. 2004;  11 43-49
  PubMedGoogle Scholar
• 90 Holick M F. Is psoriasis a T cell disease? Commentary 6.  Exp Dermatol. 2000;  9 374-375
  PubMedGoogle Scholar
• 91 Holick M F, Chimeh F N, Ray S. Topical PTH (1 - 34) is a novel, safe and effective treatment for psoriasis: a randomized self-controlled trial and an open trial.  Br J Dermatol. 2003;  149 370-376
  CrossrefPubMedGoogle Scholar
• 92 Schröder J M. Is psoriasis a T-cell disease? Viewpoint 2.  Exp Dermatol. 2000;  9 363-366
  PubMedGoogle Scholar
• 93 Nestle F O, Conrad C, Tun-Kyi A, Homey B, Gombert M, Boyman O, Burg G, Liu Y J, Gilliet M. Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production.  J Exp Med. 2005;  202 135-143
  CrossrefPubMedGoogle Scholar

Prof. Dr. Michael P. Schön

Klinik für Dermatologie, Venerologie und Allergologie und Rudolf Virchow Zentrum, DFG Forschungszentrum für Experimentelle Biomedizin · Bayerische Julius Maximilians Universität

Versbacher Str. 9 · 97078 Würzburg

Email: michael.schoen@virchow.uni-wuerzburg.de