THE ROLE OF ETANERCEPT ON THE EXPRESSION OF MARKERS OF T HELPER 17 CELLS AND THEIR PRECURSORS IN SKIN LESIONS OF PATIENTS WITH PSORIASIS VULGARIS

被引:10
作者
Antiga, E. [1 ,2 ]
Volpi, W. [1 ]
Chiarini, C. [1 ]
Cardilicchia, E. [3 ]
Fili, L. [3 ]
Manuelli, C. [1 ,3 ]
Parronchi, P. [3 ]
Fabbri, P. [1 ]
Caproni, M. [1 ]
机构
[1] Univ Florence, Dept Dermatol Sci, I-50129 Florence, Italy
[2] Univ Florence, Dept Clin Physiopathol, I-50129 Florence, Italy
[3] Univ Florence, Dept Internal Med, Ctr Res Transfer & High Educ DENOThe, I-50129 Florence, Italy
关键词
psoriasis; etanercept; CD161; ROR gamma t; CCR6; Th17; precursors; ATOPIC-DERMATITIS; NATURAL-KILLER; PATHOGENESIS; INFLAMMATION; CYTOKINES; IL-17; CCR6;
D O I
10.1177/039463201002300310
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Very recently, it has been demonstrated that CD161, retinoic acid related orphan receptor gamma t (ROR gamma t) and CC-chemokin receptor 6 (CCR6) can be considered good surface markers to detect T helper 17 cells and their precursors, T cell populations that are considered to play an important role in the pathogenesis of psoriasis. In the present study, we evaluate the clinical involvement by calculating the PASI score and the number of CD4+, CD161+, ROR gamma t+ and CCR6+ cells before and after a 12-week course with etanercept or acitretin in patients with moderate-to-severe, plaque-type psoriasis vulgaris. Ten patients were given etanercept 50 mg twice weekly and 10 patients acitretin 0.4 mg/kg per day, both for 12 weeks. At the baseline and at the end of the treatment PASI was calculated, and skin biopsies were taken to evaluate the expression of CD4, CD161, ROR gamma t and CCR6 by immunohistochemistry. As controls, 10 patients with atopic dermatitis (AD) were included in the study. After 12 weeks, PASI was significantly lower than at the baseline for both groups. However, etanercept-treated patients showed lower PASI than acitretin-treated ones. While CD4+ cell numbers were similar in both diseases, all the other markers, that are considered more specific for Th17 cells and their precursors, were more expressed in psoriasis than in AD. Furthermore, only etanercept, but not acitretin, was able to significantly reduce CD161+, ROR gamma t+ and CCR6+ cells in skin lesions of patients with psoriasis. Our study provides further evidence of the role of Th17 pathway in the pathogenesis of psoriasis. Furthermore, our findings suggest that etanercept is able to downregulate the expression of the recently recognized markers of Th17 cells and their precursors CD161, ROR gamma t and CCR6, while acitretin is not. This activity on the Th17 lineage may contribute to the efficacy of etanercept in the treatment of psoriasis.
引用
收藏
页码:767 / 774
页数:8
相关论文
共 30 条
  • [1] Phenotypic and functional features of human Th17 cells
    Annunziato, Francesco
    Cosmi, Lorenzo
    Santarlasci, Veronica
    Maggi, Laura
    Liotta, Francesco
    Mazzinghi, Benedetta
    Parente, Eliana
    Fili, Lucia
    Ferri, Simona
    Frosali, Francesca
    Giudici, Francesco
    Romagnani, Paola
    Parronchi, Paola
    Tonelli, Francesco
    Maggi, Enrico
    Romagnani, Sergio
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) : 1849 - 1861
  • [2] BOYMAN O, 2004, TRENDS IMMUNOL, V25, P295, DOI DOI 10.1016/J.IT.2004.03.006
  • [3] Natural killer and natural killer-T cells in psoriasis
    Cameron, AL
    Kirby, B
    Fei, W
    Griffiths, CEM
    [J]. ARCHIVES OF DERMATOLOGICAL RESEARCH, 2002, 294 (08) : 363 - 369
  • [4] The role of apoptosis in the pathogenesis of dermatitis herpetiformis
    Caproni, M
    Torchia, D
    Antiga, E
    Degl'Innocenti, D
    Barletta, E
    Baroni, G
    Santucci, M
    Fabbri, P
    [J]. INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY, 2005, 18 (04) : 691 - 699
  • [5] Serum Levels of IL-17 and IL-22 Are Reduced by Etanercept, but not by Acitretin, in Patients with Psoriasis: a Randomized-Controlled Trial
    Caproni, M.
    Antiga, E.
    Melani, L.
    Volpi, W.
    Del Bianco, E.
    Fabbri, P.
    [J]. JOURNAL OF CLINICAL IMMUNOLOGY, 2009, 29 (02) : 210 - 214
  • [6] Immunobiologics in the treatment of psoriasis
    Chong, Benjamin F.
    Wong, Henry K.
    [J]. CLINICAL IMMUNOLOGY, 2007, 123 (02) : 129 - 138
  • [7] Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor
    Cosmi, Lorenzo
    De Palma, Raffaele
    Santarlasci, Veronica
    Maggi, Laura
    Capone, Manuela
    Frosali, Francesca
    Rodolico, Gabriella
    Querci, Valentina
    Abbate, Gianfranco
    Angeli, Roberta
    Berrino, Liberato
    Fambrini, Massimiliano
    Caproni, Marzia
    Tonelli, Francesco
    Lazzeri, Elena
    Parronchi, Paola
    Liotta, Francesco
    Maggi, Enrico
    Romagnani, Sergio
    Annunziato, Francesco
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (08) : 1903 - 1916
  • [8] The IL-23/Th17 Axis in the Immunopathogenesis of Psoriasis
    Di Cesare, Antonella
    Di Meglio, Paola
    Nestle, Frank O.
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2009, 129 (06) : 1339 - 1350
  • [9] Molecular mechanisms of retinoid actions in skin
    Fisher, GJ
    Voorhees, JJ
    [J]. FASEB JOURNAL, 1996, 10 (09) : 1002 - 1013
  • [10] Low Expression of the IL-23/Th17 Pathway in Atopic Dermatitis Compared to Psoriasis
    Guttman-Yassky, Emma
    Lowes, Michelle A.
    Fuentes-Duculan, Judilyn
    Zaba, Lisa C.
    Cardinale, Irma
    Nograles, Kristine E.
    Khatcherian, Artemis
    Novitskaya, Inna
    Carucci, John A.
    Bergman, Reuven
    Krueger, James G.
    [J]. JOURNAL OF IMMUNOLOGY, 2008, 181 (10) : 7420 - 7427