A pathogenetic approach to autoimmune skin disease therapy: Psoriasis and biological drugs, unresolved issues, and future directions

Current Pharmaceutical Design

Volumn 17, Issue 29, 2011, Pages 3176-3190

  Ayroldi, Emira ^a   Bastianelli, Alessandra ^a   Cannarile, Lorenza ^a   Petrillo, Maria Grazia ^a   Delfino, Domenico V ^a   Fierabracci, Alessandra ^b  

^a UNIVERSITY OF PERUGIA   (Italy)

^b BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

Author keywords

Autoimmunity; Biological therapy; IL 12 IL 23 antagonists; Inflammation; Keratinocyte proliferation differentiation; Psoriasis; Psoriasis arthritis; T helper differentiation; TNF aantagonists

Indexed keywords

ADALIMUMAB; ALEFACEPT; BRIAKINUMAB; CERTOLIZUMAB PEGOL; CYCLOSPORIN; EFALIZUMAB; ETANERCEPT; GOLIMUMAB; INFLIXIMAB; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 22; INTERLEUKIN 23; METHOTREXATE; SECUKINUMAB; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; USTEKINUMAB; VASCULAR CELL ADHESION MOLECULE 1; IMMUNOLOGIC FACTOR;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ARTHRALGIA; ARTICLE; ATHEROSCLEROSIS; DENDRITIC CELL; DRY SKIN; DYSLIPIDEMIA; ENTEROPATHY; ERYTHEMA; ERYTHRODERMIC PSORIASIS; GENETIC SUSCEPTIBILITY; GUTTATE PSORIASIS; HUMAN; HYPERKERATOSIS; HYPERTENSION; INSULIN RESISTANCE; LEUKOENCEPHALOPATHY; MACROPHAGE; MYOPATHY; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PSORIASIS; PSORIASIS VULGARIS; PSORIATIC ARTHRITIS; PUSTULAR PSORIASIS; PUSTULE; REGULATORY T LYMPHOCYTE; RESPIRATORY TRACT INFECTION; RHEUMATOID ARTHRITIS; SPONDYLITIS; STREPTOCOCCUS INFECTION; T LYMPHOCYTE ACTIVATION; TH17 CELL; XEROSIS; ANIMAL; DISEASE MODEL; DRUG DELIVERY SYSTEM; DRUG DESIGN; HELPER CELL; IMMUNOLOGY; MOUSE; PATHOPHYSIOLOGY; REVIEW; T LYMPHOCYTE;

ANIMALS; DISEASE MODELS, ANIMAL; DRUG DELIVERY SYSTEMS; DRUG DESIGN; HUMANS; IMMUNOLOGIC FACTORS; MICE; PSORIASIS; T-LYMPHOCYTES; T-LYMPHOCYTES, HELPER-INDUCER; TH17 CELLS;

EID: 84858720145     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161211798157649     Document Type: Article

References (185)

1. Baker BS, Powles AV, Fry L, McFadden JP, Brent L, Valdimarsson H. Psoriatic science. Br Med J (Clin Res Ed) 1987; 295: 1562.
2. Gudjonsson JE, Johnston A, Sigmundsdottir H, Valdimarsson H. Immunopathogenic mechanisms in psoriasis. Clin Exp Immunol 2004; 135: 1-8.
3. Gyulai R, Kemeny L. The immunology of psoriasis: from basic research to the bedside. Orv Hetil 2006; 147: 2213-2220.
4. Hueber AJ, McInnes IB. Immune regulation in psoriasis and psoriatic arthritis--recent developments. Immunol Lett 2007; 114: 59-65.
5. Ritchlin C, Haas-Smith SA, Hicks D, Cappuccio J, Osterland CK, Looney RJ. Patterns of cytokine production in psoriatic synovium. J Rheumatol 1998; 25: 1544-15452.
6. Nickoloff BJ, Qin JZ, Nestle FO. Immunopathogenesis of psoriasis. Clin Rev Allergy Immunol 2007; 33: 45-56.
7. Nickoloff BJ, Xin H, Nestle FO, Qin JZ. The cytokine and chemokine network in psoriasis. Clin Dermatol 2007; 25: 568-573.
8. Robert C, Kupper TS. Inflammatory skin diseases, T cells, and immune surveillance. N Engl J Med 1999; 341: 1817-1828.
9. Lebwohl M. Psoriasis. Lancet 2003; 361: 1197-1204.
10. Veale D, Rogers S, Fitzgerald O. Classification of clinical subsets in psoriatic arthritis. Br J Rheumatol 1994; 33: 133-138.
11. Cantini F, Niccoli L, Nannini C, Kaloudi O, Bertoni M, Cassara E. Psoriatic arthritis: a systematic review. Int J Rheum Dis 2006; 13: 300-317.
12. Gaspari AA. Innate and adaptive immunity and the pathophysiology of psoriasis. J Am Acad Dermatol 2006; 54: S67-S80.
13. Fitzgerald O, Winchester R. Psoriatic arthritis: from pathogenesis to therapy. Arthritis Res Ther 2009; 11: 214.
14. Jabbari A, Johnson-Huang LM, Krueger JG. Role of the immune system and immunological circuits in psoriasis. G Ital Dermatol Venereol 2011; 146: 17-30.
15. Hirota K, Duarte JH, Veldhoen M, et al. Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol 201l; 12: 255-263.
16. Fantuzzi F, Del Giglio M, Gisondi P, Girolomoni G. Targeting tumor necrosis factor alpha in psoriasis and psoriatic arthritis. Expert Opin Ther Targets 2008; 12: 1085-1096.
17. Boker A, Kimball AB, Rolz-Cruz G. Biologicals in the treatment of psoriasis. Curr Opin Investig Drugs 2007; 8: 939-946.
18. Mossner R, Schon MP, Reich K. Tumor necrosis factor antagonists in the therapy of psoriasis. Clin Dermatol 2008; 26: 486-502.
19. Sobell JM, Weinberg JM. Patient fatalities potentially associated with efalizumab use. J Drugs Dermatol 2009; 8: 215.
20. Rozenblit M, Lebwohl M. New biologics for psoriasis and psoriatic arthritis. Dermatol Ther 2009; 22: 56-60.
21. Yun WJ, Lee DW, Chang SE, et al. Role of CD4CD25FOXP3 Regulatory T Cells in Psoriasis. Ann Dermatol 2010; 22: 397-403.
22. Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet 2007; 370: 263-271.
23. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med 2009; 361: 496-509.
24. Schon MP, Boehncke WH. Psoriasis. N Engl J Med 2005; 352: 1899-1912.
25. Jones SM, Armas JB, Cohen MG, Lovell CR, Evison G, McHugh NJ. Psoriatic arthritis: outcome of disease subsets and relationship of joint disease to nail and skin disease. Br J Rheumatol 1994; 33: 834-839.
26. Naldi L, Rzany B. Chronic plaque psoriasis. Clin Evid 2002: 1688-1708.
27. K. Chronic plaque psoriasis: an overview. Nurs Stand 2002; 16: 45-52; quiz 54-45.
28. Christophers E, Kiene P. Guttate and plaque psoriasis. Dermatol Clin 1995; 13: 751-756.
29. Prystowsky JH, Cohen PR. Pustular and erythrodermic psoriasis. Dermatol Clin 1995; 13: 757-770.
30. Radtke MA, Reich K, Blome C, Rustenbach S, Augustin M. Prevalence and clinical features of psoriatic arthritis and joint complaints in 2009 patients with psoriasis: results of a German national survey. J Eur Acad Dermatol Venereol 2009; 23: 683-91.
31. Gladman DD. Psoriatic arthritis. Dermatol Ther 2009; 22: 40-55.
32. Nograles KE, Brasington RD, Bowcock AM. New insights into the pathogenesis and genetics of psoriatic arthritis. Nat Clin Pract Rheumatol 2009; 5: 83-91.
33. Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006; 54: 2665-73.
34. Helliwell PS, Porter G, Taylor WJ. Polyarticular psoriatic arthritis is more like oligoarticular psoriatic arthritis, than rheumatoid arthritis. Ann Rheum Dis 2007; 66: 113-7.
35. Salvarani C, Macchioni P, Cremonesi T, et al. The cervical spine in patients with psoriatic arthritis: a clinical, radiological and immu-nogenetic study. Ann Rheum Dis 1992; 51: 73-7.
36. Chandran V, Barrett J, Schentag CT, Farewell VT, Gladman DD. Axial psoriatic arthritis: update on a longterm prospective study. J Rheumatol 2009; 36: 2744-50.
37. McGonagle D, Marzo-Ortega H, O'Connor P, et al. Histological assessment of the early enthesitis lesion in spondyloarthropathy. Ann Rheum Dis 2002; 61: 534-7.
38. Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis 2003; 62: 127-32.
39. Gottlieb AB, Dann F. Comorbidities in patients with psoriasis. Am J Med 2009; 122: 1150 e1151-9.
40. Gladman DD, Ang M, Su L, Tom BD, Schentag CT, Farewell VT. Cardiovascular morbidity in psoriatic arthritis. Ann Rheum Dis 2009; 68: 1131-5.
41. Marchesoni A, Helliwell P, Gallazzi M, Gibertini P, Rossetti A, Galli L. Psoriatic arthritis in British and Italian patients: a comparative clinical, radiologic, and scintigraphic study. J Rheumatol 1999; 26: 2619-21.
42. Fredriksson T, Pettersson U. Severe psoriasis--oral therapy with a new retinoid. Dermatologica 1978; 157: 238-44.
43. Smith CH, Anstey AV, Barker JN, et al. British Association of Dermatologists' guidelines for biologic interventions for psoriasis 2009. Br J Dermatol 2009; 161: 987-1019.
44. Pathirana D, Ormerod AD, Saiag P, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Derma-tol Venereol 2009; 23 (Suppl 2): 1-70.
45. Bowes J, Barton A. The genetics of psoriatic arthritis: lessons from genome-wide association studies. Discov Med 2010; 10: 177-83.
46. O'Rielly DD, Rahman P. Where do we stand with the genetics of psoriatic arthritis? Curr Rheumatol Rep 2010; 12: 300-8.
47. Liu Y, Krueger JG, Bowcock AM. Psoriasis: genetic associations and immune system changes. Genes Immun 2007; 8: 1-12.
48. Valdimarsson H, Thorleifsdottir RH, Sigurdardottir SL, Gudjonsson JE, Johnston A. Psoriasis--as an autoimmune disease caused by molecular mimicry. Trends Immunol 2009; 30: 494-501.
49. Nair RP, Stuart PE, Nistor I, et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet 2006; 78: 827-51.
50. Bowcock AM, Krueger JG. Getting under the skin: the immunoge-netics of psoriasis. Nat Rev Immunol 2005; 5: 699-711.
51. Costello P, Bresnihan B, O'Farrelly C, FitzGerald O. Predominance of CD8+ T lymphocytes in psoriatic arthritis. J Rheumatol 1999; 26: 1117-24.
52. Valdimarsson H. The genetic basis of psoriasis. Clin Dermatol 2007; 25: 563-7.
53. Prinz JC. Psoriasis vulgaris--a sterile antibacterial skin reaction mediated by cross-reactive T cells? An immunological view of the pathophysiology of psoriasis. Clin Exp Dermatol 2001; 26: 326-32.
54. Baker BS, Laman JD, Powles A, et al. Peptidoglycan and pepti-doglycan-specific Th1 cells in psoriatic skin lesions. J Pathol 2006; 209: 174-81.
55. Baker BS, Powles A, Fry L. Peptidoglycan: a major aetiological factor for psoriasis? Trends Immunol 2006; 27: 545-51.
56. Gudjonsson JE, Thorarinsson AM, Sigurgeirsson B, Kristinsson KG, Valdimarsson H. Streptococcal throat infections and exacerbation of chronic plaque psoriasis: a prospective study. Br J Dermatol 2003; 149: 530-4.
57. Ovigne JM, Baker BS, Davison SC, Powles AV, Fry L. Epidermal CD8+ T cells reactive with group A streptococcal antigens in chronic plaque psoriasis. Exp Dermatol 2002; 11: 357-64.
58. Gudmundsdottir AS, Sigmundsdottir H, Sigurgeirsson B, Good MF, Valdimarsson H, Jonsdottir I. Is an epitope on keratin 17 a major target for autoreactive T lymphocytes in psoriasis? Clin Exp Immunol 1999; 117: 580-6.
59. Zenz R, Eferl R, Kenner L, et al. Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins. Nature 2005; 437: 369-75.
60. Zenz R, Wagner EF. Jun signalling in the epidermis: From developmental defects to psoriasis and skin tumors. Int J Biochem Cell Biol 2006; 38: 1043-9.
61. Shen Q, Bai Y, Chang KC, et al. Liver X receptor-retinoid X receptor (LXR-RXR) heterodimer cistrome reveals coordination of LXR and AP1 signaling in keratinocytes. J Biol Chem 2011; 286: 14554-63.
62. Wolf R, Mascia F, Dharamsi A, et al. Gene from a psoriasis susceptibility locus primes the skin for inflammation. Sci Transl Med 2010; 2: 61-90.
63. Warren RB, Smith RL, Flynn E, et al. A systematic investigation of confirmed autoimmune loci in early-onset psoriasis reveals an association with IL2/IL21. Br J Dermatol 2011; 164: 660-664.
64. Stuart PE, Nair RP, Ellinghaus E, et al. Genome-wide association analysis identifies three psoriasis susceptibility loci. Nat Genet 2010; 42: 1000-1004.
65. Sun LD, Cheng H, Wang ZX, et al. Association analyses identify six new psoriasis susceptibility loci in the Chinese population. Nat Genet 2010; 42: 1005-1009.
66. Woolf RT, Smith CH. How genetic variation affects patient response and outcome to therapy for psoriasis. Expert Rev Clin Immunol 2010; 6: 957-966.
67. Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 2007; 445: 866-873.
68. Mossner R, Kingo K, Kleensang A, et al. Association of TNF -238 and -308 promoter polymorphisms with psoriasis vulgaris and pso-riatic arthritis but not with pustulosis palmoplantaris. J Invest Der-matol 2005; 124: 282-284.
69. Nickoloff BJ, Karabin GD, Barker JN, et al. Cellular localization of interleukin-8 and its inducer, tumor necrosis factor-alpha in psoriasis. Am J Pathol 1991; 138: 129-140.
70. Uyemura K, Yamamura M, Fivenson DF, Modlin RL, Nickoloff BJ. The cytokine network in lesional and lesion-free psoriatic skin is characterized by a T-helper type 1 cell-mediated response. J Invest Dermatol 1993; 101: 701-705.
71. Austin LM, Ozawa M, Kikuchi T, Walters IB, Krueger JG. The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients. J Invest Dermatol 1999; 113: 752-759.
72. Ferenczi K, Burack L, Pope M, Krueger JG, Austin LM. CD69, HLA-DR and the IL-2R identify persistently activated T cells in psoriasis vulgaris lesional skin: blood and skin comparisons by flow cytometry. J Autoimmun 2000; 14: 63-78.
73. Schlaak JF, Buslau M, Jochum W, et al. T cells involved in psoriasis vulgaris belong to the Th1 subset. J Invest Dermatol 1994; 102: 145-149.
74. Nickoloff BJ, Nestle FO. Recent insights into the immunopatho-genesis of psoriasis provide new therapeutic opportunities. J Clin Invest 2004; 113: 1664-1675.
75. Iwakura Y, Ishigame H. The IL-23/IL-17 axis in inflammation. J Clin Invest 2006; 116: 1218-1222.
76. Kolls JK, Linden A. Interleukin-17 family members and inflammation. Immunity 2004; 21: 467-476.
77. Toichi E, Torres G, McCormick TS, et al. An anti-IL-12p40 antibody down-regulates type 1 cytokines, chemokines, and IL-12/IL-23 in psoriasis. J Immunol 2006; 177: 4917-4926.
78. Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol 2009; 10: 857-863.
79. Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A. Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol 2010; 130: 1373-1383.
80. Lande R, Gregorio J, Facchinetti V, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 2007; 449: 564-569.
81. Kopf M, Bachmann MF, Marsland BJ. Averting inflammation by targeting the cytokine environment. Nat Rev Drug Discov 2010; 9: 703-718.
82. Steinman L. Immune therapy for autoimmune diseases. Science 2004; 305: 212-216.
83. Weger W. Current status and new developments in the treatment of psoriasis and psoriatic arthritis with biological agents. Br J Pharmacol 2010; 160: 810-820.
84. C. Psoriasis and Biologics. Introduction. Semin Cutan Med Surg 2010; 29: 1-2.
85. Appleman LJ, Boussiotis VA. T cell anergy and costimulation. Immunol Rev 2003; 192: 161-180.
86. Podojil JR, Miller SD. Molecular mechanisms of T-cell receptor and costimulatory molecule ligation/blockade in autoimmune disease therapy. Immunol Rev 2009; 229: 337-355.
87. Raychaudhuri SP, Kundu-Raychaudhuri S, Tamura K, et al. FR255734, a humanized, Fc-Silent, Anti-CD28 antibody, improves psoriasis in the SCID mouse-psoriasis xenograft model. J Invest Dermatol 2008; 128: 1969-1976.
88. Sugiyama H, McCormick TS, Cooper KD, Korman NJ. Alefacept in the treatment of psoriasis. Clin Dermatol 2008; 26: 503-508.
89. Heffernan MP, Leonardi CL. Alefacept for psoriasis. Semin Cutan Med Surg 2010; 29: 53-55.
90. Gordon KB, Vaishnaw AK, O'Gorman J, Haney J, Menter A. Treatment of psoriasis with alefacept: correlation of clinical improvement with reductions of memory T-cell counts. Arch Derma-tol 2003; 139: 1563-1570.
91. Ortonne JP, Lebwohl M, Em Griffiths C. Alefacept-induced decreases in circulating blood lymphocyte counts correlate with clinical response in patients with chronic plaque psoriasis. Eur J Derma-tol 2003; 13: 117-123.
92. Ortonne JP, Prinz JC. Alefacept: a novel and selective biologic agent for the treatment of chronic plaque psoriasis. Eur J Dermatol 2004; 14: 41-45.
93. Sobell JM, Kalb RE, Weinberg JM. Management of moderate to severe plaque psoriasis (part 2): clinical update on T-cell modulators and investigational agents. J Drugs Dermatol 2009; 8: 230-238.
94. Sobell JM, Kalb RE, Weinberg JM. Management of moderate to severe plaque psoriasis (part I): clinical update on antitumor necrosis factor agents. J Drugs Dermatol 2009; 8: 147-154.
95. Boehncke WH. Efalizumab in the treatment of psoriasis. Biologics 2007; 1: 301-309.
96. Schon MP. Efalizumab in the treatment of psoriasis: mode of action, clinical indications, efficacy, and safety. Clin Dermatol 2008; 26: 509-514.
97. Selenko-Gebauer N, Karlhofer F, Stingl G. Efalizumab in routine use: a clinical experience. Br J Dermatol 2007; 156 (Suppl 2): 1-6.
98. Koszik F, Stary G, Selenko-Gebauer N, Stingl G. Efalizumab modulates T cell function both in vivo and in vitro. J Dermatol Sci 2010; 60: 159-166.
99. Kuschei WM, Leitner J, Majdic O, et al. Costimulatory signals potently modulate the T cell inhibitory capacity of the therapeutic CD11a antibody Efalizumab. Clin Immunol 2011; 139: 199-207.
100. Weinberg JM, Saini R, Tutrone WD. Biologic therapy for psoria-sis--the first wave: infliximab, etanercept, efalizumab, and ale-facept. J Drugs Dermatol 2002; 1: 303-310.
101. Korman BD, Tyler KL, Korman NJ. Progressive multifocal leu-koencephalopathy, efalizumab, and immunosuppression: a cautionary tale for dermatologists. Arch Dermatol 2009; 145: 937-942.
102. Hansel A, Gunther C, Ingwersen J, et al. Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong T(h)17/T(h)1 T-cell responses. J Allergy Clin Immunol 2011; 127: 787-794 e789.
103. Lowes MA, Kikuchi T, Fuentes-Duculan J, et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol 2008; 128: 1207-1211.
104. Zaba LC, Fuentes-Duculan J, Eungdamrong NJ, et al. Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells. J Invest Dermatol 2009; 129: 79-88.
105. Miossec P. IL-17 and Th17 cells in human inflammatory diseases. Microbes Infect 2009; 11: 625-630.
106. Miossec P. Diseases that may benefit from manipulating the Th17 pathway. Eur J Immunol 2009; 39: 667-669.
107. Bazzoni F, Beutler B. The tumor necrosis factor ligand and receptor families. N Engl J Med 1996; 334: 1717-1725.
108. Smookler DS, Mohammed FF, Kassiri Z, Duncan GS, Mak TW, Khokha R. Tissue inhibitor of metalloproteinase 3 regulates TNF-dependent systemic inflammation. J Immunol 2006; 176: 721-725.
109. Chan FK, Chun HJ, Zheng L, Siegel RM, Bui KL, Lenardo MJ. A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science 2000; 288: 2351-2354.
110. Schottelius AJ, Moldawer LL, Dinarello CA, Asadullah K, Sterry W, Edwards CK, 3rd. Biology of tumor necrosis factor-alpha- implications for psoriasis. Exp Dermatol 2004; 13: 193-222.
111. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 2008; 117: 244-279.
112. Feldmann M, Maini RN. Discovery of TNF-alpha as a therapeutic target in rheumatoid arthritis: preclinical and clinical studies. Joint Bone Spine 2002; 69: 12-18.
113. Kristensen M, Chu CQ, Eedy DJ, Feldmann M, Brennan FM, Breathnach SM. Localization of tumour necrosis factor-alpha (TNF-alpha) and its receptors in normal and psoriatic skin: epidermal cells express the 55-kD but not the 75-kD TNF receptor. Clin Exp Immunol 1993; 94: 354-362.
114. Alexopoulou L, Pasparakis M, Kollias G. A murine transmembrane tumor necrosis factor (TNF) transgene induces arthritis by cooperative p55/p75 TNF receptor signaling. Eur J Immunol 1997; 27: 2588-2592.
115. Zwerina J, Hayer S, Tohidast-Akrad M, et al. Single and combined inhibition of tumor necrosis factor, interleukin-1, and RANKL pathways in tumor necrosis factor-induced arthritis: effects on synovial inflammation, bone erosion, and cartilage destruction. Arthritis Rheum 2004; 50: 277-290.
116. Redlich K, Gortz B, Hayer S, et al. Repair of local bone erosions and reversal of systemic bone loss upon therapy with anti-tumor necrosis factor in combination with osteoprotegerin or parathyroid hormone in tumor necrosis factor-mediated arthritis. Am J Pathol 2004; 164: 543-555.
117. Boyman O, Hefti HP, Conrad C, Nickoloff BJ, Suter M, Nestle FO. 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.
118. Gudjonsson JE, Johnston A, Dyson M, Valdimarsson H, Elder JT. Mouse models of psoriasis. J Invest Dermatol 2007; 127: 1292-1308.
119. Ferrandiz C, Carrascosa JM, Boada A. A new era in the management of psoriasis? The biologics: facts and controversies. Clin Dermatol 2010; 28: 81-87.
120. Kircik LH, Del Rosso JQ. Anti-TNF agents for the treatment of psoriasis. J Drugs Dermatol 2009; 8: 546-559.
121. Koutruba N, Emer J, Lebwohl M. Review of ustekinumab, an inter-leukin-12 and interleukin-23 inhibitor used for the treatment of plaque psoriasis. Ther Clin Risk Manag 2010; 6: 123-141.
122. Scallon B, Cai A, Solowski N, et al. Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther 2002; 301: 418-426.
123. Scallon BJ, Moore MA, Trinh H, Knight DM, Ghrayeb J. Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine 1995; 7: 251-259.
124. Mitoma H, Horiuchi T, Tsukamoto H. Binding activities of inflixi-mab and etanercept to transmembrane tumor necrosis factor-alpha. Gastroenterology 2004; 126: 934-935; author reply 935-6.
125. Mitoma H, Horiuchi T, Hatta N, et al. Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-alpha. Gastroenterology 2005; 128: 376-392.
126. Harashima S, Horiuchi T, Hatta N, et al. Outside-to-inside signal through the membrane TNF-alpha induces E-selectin (CD62E) expression on activated human CD4+ T cells. J Immunol 2001; 166: 130-136.
127. Monastra G, Cabrelle A, Zambon A, et al. Membrane form of TNF alpha induces both cell lysis and apoptosis in susceptible target cells. Cell Immunol 1996; 171: 102-110.
128. Eissner G, Kirchner S, Lindner H, et al. Reverse signaling through transmembrane TNF confers resistance to lipopolysaccharide in human monocytes and macrophages. J Immunol 2000; 164: 6193-6198.
129. Goedkoop AY, Kraan MC, Teunissen MB, et al. Early effects of tumour necrosis factor alpha blockade on skin and synovial tissue in patients with active psoriasis and psoriatic arthritis. Ann Rheum Dis 2004; 63: 769-773.
130. Kruger-Krasagakis S, Galanopoulos VK, Giannikaki L, Stefanidou M, Tosca AD. Programmed cell death of keratinocytes in inflixi-mab-treated plaque-type psoriasis. Br J Dermatol 2006; 154: 460-466.
131. Malaviya R, Sun Y, Tan JK, et al. Etanercept induces apoptosis of dermal dendritic cells in psoriatic plaques of responding patients. J Am Acad Dermatol 2006; 55: 590-597.
132. Gottlieb AB, Chamian F, Masud S, et al. TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques. J Immunol 2005; 175: 2721-2729.
133. Gomez-Reino JJ, Carmona L. Switching TNF antagonists in patients with chronic arthritis: an observational study of 488 patients over a four-year period. Arthritis Res Ther 2006; 8: R29.
134. Boyce BF, Li P, Yao Z, et al. TNF-alpha and pathologic bone re-sorption. Keio J Med 2005; 54: 127-131.
135. Keffer J, Probert L, Cazlaris H, et al. Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J 1991; 10: 4025-4031.
136. Nadkarni S, Mauri C, Ehrenstein MR. Anti-TNF-alpha therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-beta. J Exp Med 2007; 204: 33-39.
137. Sugiyama H, Gyulai R, Toichi E, et al. Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. J Immunol 2005; 174: 164-173.
138. Shen Z, Chen L, Hao F, Wang G, Liu Y. Intron-1 rs3761548 is related to the defective transcription of Foxp3 in psoriasis through abrogating E47/c-Myb binding. J Cell Mol Med 2010; 14: 226-241.
139. Diluvio L, Romiti ML, Angelini F, et al. Infliximab therapy induces increased polyclonality of CD4+CD25+ regulatory T cells in psoriasis. Br J Dermatol 2010; 162: 895-897.
140. Ma HL, Napierata L, Stedman N, et al. Tumor necrosis factor alpha blockade exacerbates murine psoriasis-like disease by enhancing Th17 function and decreasing expansion of Treg cells. Arthritis Rheum 2010; 62: 430-440.
141. Zaba LC, Suarez-Farinas M, Fuentes-Duculan J, et al. Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes. J Allergy Clin Immunol 2009; 124: 1022-1110 e1021-395.
142. Asarch A, Barak O, Loo DS, Gottlieb AB. Th17 cells: a new therapeutic target in inflammatory dermatoses. J Dermatol Treat 2008; 19: 318-326.
143. Zheng Y, Valdez PA, Danilenko DM, et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 2008; 14: 282-289.
144. Qian Y, Kang Z, Liu C, Li X. IL-17 signaling in host defense and inflammatory diseases. Cell Mol Immunol 2010; 7: 328-333.
145. Mai J, Wang H, Yang XF. Th 17 cells interplay with Foxp3+ Tregs in regulation of inflammation and autoimmunity. Front Biosci 2010; 15: 986-1006.
146. van der Fits L, Mourits S, Voerman JS, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol 2009; 182: 5836-45.
147. Haider AS, Lowes MA, Suarez-Farinas M, et al. Identification of cellular pathways of type 1, Th17 T cells, and TNF- and induc-ible nitric oxide synthase-producing dendritic cells in autoimmune inflammation through pharmacogenomic study of cyclosporine A in psoriasis. J Immunol 2008; 180: 1913-20.
148. Wolk K, Witte E, Wallace E, et al. IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 2006; 36: 1309-23.
149. Sabat R, Wolk K. Research in practice: IL-22 and IL-20: significance for epithelial homeostasis and psoriasis pathogenesis. J Dtsch Dermatol Ges 2011 [Epub ahead of print].
150. Res PC, Piskin G, de Boer OJ, et al. Overrepresentation of IL-17A and IL-22 producing CD8 T cells in lesional skin suggests their involvement in the pathogenesis of psoriasis. PLoS One 2010; 5: e14108.
151. Gregersen PK, Olsson LM. Recent advances in the genetics of autoimmune disease. Annu Rev Immunol 2009; 27: 363-391.
152. Zaba LC, Cardinale I, Gilleaudeau P, et al. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J Exp Med 2007; 204: 3183-3194.
153. Tohyama M, Hanakawa Y, Shirakata Y, et al. IL-17 and IL-22 mediate IL-20 subfamily cytokine production in cultured keratinocytes via increased IL-22 receptor expression. Eur J Immunol 2009; 39: 2779-2788.
154. Lowes MA, Chamian F, Abello MV, et al. Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). Proc Natl Acad Sci USA 2005; 102: 19057-19062.
155. Chan JR, Blumenschein W, Murphy E, et al. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. J Exp Med 2006; 203: 2577-2587.
156. Nakajima A, Matsuki T, Komine M, et al. TNF, but not IL-6 and IL-17, is crucial for the development of T cell-independent psoriasis-like dermatitis in Il1rn-/- mice. J Immunol 2010; 185: 1887-1893.
157. Guilloteau K, Paris I, Pedretti N, et al. Skin Inflammation Induced by the Synergistic Action of IL-17A, IL-22, Oncostatin M, IL-1{alpha}, and TNF-{alpha} Recapitulates Some Features of Psoriasis. J Immunol 2010; 184: 5263-5270.
158. Eyerich S, Eyerich K, Pennino D, et al. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest 2009; 119: 3573-3585.
159. Reddy M, Torres G, McCormick T, et al. Positive treatment effects of ustekinumab in psoriasis: analysis of lesional and systemic parameters. J Dermatol 2010; 37: 413-425.
160. Martin S, Feldman SR, Augustin M, Szapary P, Schenkel B. Cost per responder analysis of ustekinumab and etanercept for moderate to severe plaque psoriasis. J Dermatol Treat 2011; 22: 138-143.
161. Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008; 371: 1675-1684.
162. Meeran SM, Punathil T, Katiyar SK. IL-12 deficiency exacerbates inflammatory responses in UV-irradiated skin and skin tumors. J Invest Dermatol 2008; 128: 2716-2727.
163. Kurzeja M, Rudnicka L, Olszewska M. New interleukin-23 pathway inhibitors in dermatology: ustekinumab, briakinumab, and secukinumab. Am J Clin Dermatol 2011; 12: 113-125.
164. Albanesi C, Scarponi C, Bosisio D, Sozzani S, Girolomoni G. Immune functions and recruitment of plasmacytoid dendritic cells in psoriasis. Autoimmunity 2010; 43: 215-219.
165. Nograles KE, Zaba LC, Shemer A, et al. IL-22-producing T22 T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol 2009; 123: 1244-1252 e1242.
166. Trifari S, Spits H. IL-22-producing CD4+ T cells: middle-men between the immune system and its environment. Eur J Immunol 2010; 40: 2369-2371.
167. Zhang N, Pan HF, Ye DQ. Th22 in inflammatory and autoimmune disease: prospects for therapeutic intervention. Mol Cell Biochem 2011; 353: 41-46.
168. Fujita H, Nograles KE, Kikuchi T, Gonzalez J, Carucci JA, Krueger JG. Human Langerhans cells induce distinct IL-22-producing CD4+ T cells lacking IL-17 production. Proc Natl Acad Sci USA 2009; 106: 21795-21800.
169. Sestito R, Madonna S, Scarponi C, et al. STAT3-dependent effects of IL-22 in human keratinocytes are counterregulated by sirtuin 1 through a direct inhibition of STAT3 acetylation. FASEB J 2011; 25: 916-927.
170. Sano S, Chan KS, Carbajal S, et al. Stat3 links activated keratino-cytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat Med 2005; 11: 43-49.
171. Miyoshi K, Takaishi M, Nakajima K, et al. Stat3 as a therapeutic target for the treatment of psoriasis: a clinical feasibility study with STA-21, a Stat3 inhibitor. J Invest Dermatol 2011; 131: 108-117.
172. Liu Y, Lagowski JP, Gao S, Raymond JH, White CR, Kulesz-Martin MF. Regulation of the psoriatic chemokine CCL20 by E3 ligases Trim32 and Piasy in keratinocytes. J Invest Dermatol 2010; 130: 1384-1390.
173. Maioli E, Valacchi G. Rottlerin: bases for a possible usage in psoriasis. Curr Drug Metab 2010; 11: 425-430.
174. Cho YC, You SK, Kim HJ, Cho CW, Lee IS, Kang BY. Xantho-humol inhibits IL-12 production and reduces chronic allergic contact dermatitis. Int Immunopharmacol 2010; 10: 556-561.
175. Huh JR, Leung MW, Huang P, et al. Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORgammat activity. Nature 2011; 472: 486-490.
176. Roybal JL, Endo M, Radu A, Zoltick PW, Flake AW. Early gesta-tional gene transfer of IL-10 by systemic administration of lentivi-ral vector can prevent arthritis in a murine model. Gene Ther 2011 [Epub ahead of print].
177. Bak RO, Stenderup K, Rosada C, et al. Targeting of human inter-leukin-12B by small hairpin RNAs in xenografted psoriatic skin. BMC Dermatol 2011; 11: 5.
178. Chang T, Sun L, Wang Y, et al. Inhibition of keratin 17 expression with antisense and RNAi strategies: exploring novel therapy for psoriasis. Exp Dermatol 2011 [Epub ahead of print].
179. D'Adamio F, Zollo O, Moraca R, et al. A new dexamethasone-induced gene of the leucine zipper family protects T lymphocytes from TCR/CD3-activated cell death. Immunity 1997; 7: 803-812.
180. Ayroldi E, Riccardi C. Glucocorticoid-induced leucine zipper (GILZ): a new important mediator of glucocorticoid action. FASEB J 2009; 23: 3649-3658.
181. Ayroldi E, Migliorati G, Bruscoli S, et al. Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappaB. Blood 2001; 98: 743-753.
182. Ayroldi E, Zollo O, Macchiarulo A, Di Marco B, Marchetti C, Ric-cardi C. Glucocorticoid-induced leucine zipper inhibits the Raf-extracellular signal-regulated kinase pathway by binding to Raf-1. Mol Cell Biol 2002; 22: 7929-7941.
183. Ayroldi E, Zollo O, Bastianelli A, et al. GILZ mediates the antipro-liferative activity of glucocorticoids by negative regulation of Ras signaling. J Clin Invest 2007; 117: 1605-1615.
184. Cannarile L, Fallarino F, Agostini M, et al. Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines. Blood 2006; 107: 1039-1047.
185. Cannarile L, Cuzzocrea S, Santucci L, et al. Glucocorticoid-induced leucine zipper is protective in Th1-mediated models of colitis. Gastroenterology 2009; 136: 530-541.