Interleukin-20 plays a critical role in maintenance and development of psoriasis in the human xenograft transplantation model

被引:53
作者
Stenderup, K. [1 ]
Rosada, C. [1 ]
Worsaae, A. [3 ]
Dagnaes-Hansen, F. [4 ]
Steiniche, T. [2 ]
Hasselager, E. [3 ]
Iversen, L. F. [3 ]
Zahn, S. [3 ]
Woldike, H. [3 ]
Lindgreen Holmberg, H. [3 ]
Romer, J. [3 ]
Kragballe, K. [1 ]
Clausen, J. T. [3 ]
Dam, T. N. [5 ]
机构
[1] Aarhus Univ Hosp, Dept Dermatol, DK-8000 Aarhus, Denmark
[2] Aarhus Univ Hosp, Dept Pathol, DK-8000 Aarhus, Denmark
[3] Novo Nordisk AS, Discovery, DK-2880 Bagsvaerd, Denmark
[4] Univ Aarhus, Dept Med Microbiol & Immunol, Aarhus, Denmark
[5] Roskilde Hosp, Dept Dermatol, Roskilde, Denmark
关键词
interleukin-20; psoriasis; SCID mice; HUMAN SKIN; CYCLOSPORINE-A; CUTTING EDGE; T-CELLS; IN-VIVO; IL-20; MOUSE; CYTOKINES; KERATINOCYTES; IMMUNOCYTES;
D O I
10.1111/j.1365-2133.2008.08890.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Interleukin (IL)-20 is a recently discovered cytokine displaying increased levels in psoriatic lesions. Interestingly, IL-20 levels decrease with antipsoriatic treatment, correlating with clinical improvement. However, the role of IL-20 in the aetiology of psoriasis is unknown. In this study, we investigate the effects both of blocking IL-20 signalling in psoriatic plaques and of adding IL-20 to nonlesional psoriasis skin. We employed the human skin xenograft transplantation model in which psoriatic plaques and nonlesional keratome skin biopsies obtained from donors with moderate to severe plaque psoriasis were transplanted on to immuno-deficient mice. The transplanted mice were treated with anti-IL-20 antibodies or recombinant human IL-20. We demonstrate that blocking IL-20 signalling with anti-IL-20 antibodies induces psoriasis resolution and inhibits psoriasis induction. We also demonstrate that continuous IL-20 infusion, together with injection of additional nonactivated leucocytes, promotes induction of psoriasis in nonlesional skin from patients with psoriasis. The results suggest that IL-20 plays a critical role in the induction and maintenance of psoriasis, and IL-20 is suggested as a new possible specific target in psoriasis treatment.
引用
收藏
页码:284 / 296
页数:13
相关论文
共 44 条
[1]   Interleukin 20: Discovery, receptor identification, and role in epidermal function [J].
Blumberg, H ;
Conklin, D ;
Xu, WF ;
Grossmann, A ;
Brender, T ;
Carollo, S ;
Eagan, M ;
Foster, D ;
Haldeman, BA ;
Hammond, A ;
Haugen, H ;
Jelinek, L ;
Kelly, JD ;
Madden, K ;
Maurer, MF ;
Parrish-Novak, J ;
Prunkard, D ;
Sexson, S ;
Sprecher, C ;
Waggie, K ;
West, J ;
Whitmore, TE ;
Yao, L ;
Kuechle, MK ;
Dale, BA ;
Chandrasekher, YA .
CELL, 2001, 104 (01) :9-19
[2]   PSORIASIFORM ARCHITECTURE OF MURINE EPIDERMIS OVERLYING HUMAN PSORIATIC DERMIS TRANSPLANTED ONTO SCID MICE [J].
BOEHNCKE, WH ;
STERRY, W ;
HAINZL, A ;
SCHEFFOLD, W ;
KAUFMANN, R .
ARCHIVES OF DERMATOLOGICAL RESEARCH, 1994, 286 (06) :325-330
[3]   The SCID-hu xenogeneic transplantation model allows screening of anti-psoriatic drugs [J].
Boehncke, WH ;
Kock, M ;
Hardt-Weinelt, K ;
Wolter, M ;
Kaufmann, R .
ARCHIVES OF DERMATOLOGICAL RESEARCH, 1999, 291 (2-3) :104-106
[4]  
Boniface K, 2005, EUR CYTOKINE NETW, V16, P309
[5]   Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-α [J].
Boyman, O ;
Hefti, HP ;
Conrad, C ;
Nickoloff, BJ ;
Suter, M ;
Nestle, FO .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (05) :731-736
[6]   IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis [J].
Chan, Jason R. ;
Blumenschein, Wendy ;
Murphy, Erin ;
Diveu, Caroline ;
Wiekowski, Maria ;
Abbondanzo, Susan ;
Lucian, Linda ;
Geissler, Richard ;
Brodie, Scott ;
Kimball, Alexa B. ;
Gorman, Daniel M. ;
Smith, Kathleen ;
Malefyt, Rene de Waal ;
Kastelein, Robert A. ;
McClanahan, Terrill K. ;
Bowman, Edward P. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (12) :2577-2587
[7]   IL-20 is expressed in atherosclerosis plaques and promotes atherosclerosis in apolipoprotein E-deficient mice [J].
Chen, Wei-Yu ;
Cheng, Bor-Chih ;
Jiang, Meei-Jyh ;
Hsieh, Mei-Yi ;
Chang, Ming-Shi .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (09) :2090-2095
[8]  
Curry JL, 2003, ARCH PATHOL LAB MED, V127, P289
[9]   1α,25-Dihydroxycholecalciferol and cyclosporine suppress induction and promote resolution of psoriasis in human skin grafts transplanted on to SCID mice [J].
Dam, TN ;
Kang, S ;
Nickoloff, BJ ;
Voorhees, JJ .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1999, 113 (06) :1082-1089
[10]   Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types [J].
Dumoutier, L ;
Leemans, C ;
Lejeune, D ;
Kotenko, SV ;
Renauld, JC .
JOURNAL OF IMMUNOLOGY, 2001, 167 (07) :3545-3549