Etanercept Downregulates the Th17 Pathway and Decreases the IL-17+/IL-10+ Cell Ratio in Patients with Psoriasis Vulgaris

被引:28
作者
Antiga, Emiliano [1 ,2 ,3 ]
Volpi, Walter [2 ]
Cardilicchia, Elisa [4 ]
Maggi, Laura [4 ]
Fili, Lucia [4 ]
Manuelli, Cinzia [2 ,4 ]
Parronchi, Paola [4 ]
Fabbri, Paolo [2 ]
Caproni, Marzia [2 ]
机构
[1] Univ Florence, Dept Med & Surg Crit Care, Dermatol Sect, I-50129 Florence, Italy
[2] Univ Florence, Dept Med & Surg Crit Care, Sect Clin Allergoimmunol & Infettivol Dermatol, I-50129 Florence, Italy
[3] Univ Florence, Dept Clin Physiopathol, I-50129 Florence, Italy
[4] Univ Florence, Ctr Res Transfer & High Educ DENOthe, I-50129 Florence, Italy
关键词
Psoriasis; etanercept; acitretin; T helper 17 cells; IL-10(+) cells; T-CELLS; RHEUMATOID-ARTHRITIS; CYTOKINES; THERAPY; IL-17; EXPRESSION; INDUCTION; MECHANISM; LESIONS; FAMILY;
D O I
10.1007/s10875-012-9716-x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To evaluate circulating and lesional CD4(+) and CD8(+) cells belonging to Th1, Th2, and Th17 patterns as well as IL-10(+) cells before and after a 12-week lasting course with etanercept or acitretin in patients with psoriasis. 15 patients were given etanercept 50 mg twice weekly and 15 patients acitretin 0,4 mg/kg/day, both for 12 weeks. At the baseline and at the end of the treatment, blood and skin samples were taken to investigate IL-4, IL-8, IL-10, IL-17, and IFN-gamma-producing CD4(+) and CD8(+) cells. As controls, 10 healthy controls (HC) and 6 atopic dermatitis (AD) patients were included into the study. Psoriasis patients showed augmented IL-17- and IL-8-producing CD4(+) cells in the blood than HC and AD patients. In the skin lesions, IL-17(+) cells were more represented in psoriasis than in AD, while the number of IL-4-producing cells was reduced in psoriasis patients than in AD ones. Etanercept was able to significantly reduce the number of IL-17- and IL-8-producing CD4(+) and CD8(+) cells both in skin and blood, as well as to augment the proportion of IL-10-producing CD4(+) cells in the skin of psoriatic patients, while acitretin was not. Our results confirmed the role of Th17 cells in the pathogenesis of psoriasis. Etanercept, but not acitretin, was able to downregulate the Th17 pathway and to increase the percentages of IL-10-producing cells in the skin.
引用
收藏
页码:1221 / 1232
页数:12
相关论文
共 40 条
  • [31] Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis:: Mechanism underlying unrestrained pathogenic effector T cell proliferation
    Sugiyama, H
    Gyulai, R
    Toichi, E
    Garaczi, E
    Shimada, S
    Stevens, SR
    McCormick, TS
    Cooper, KD
    [J]. JOURNAL OF IMMUNOLOGY, 2005, 174 (01) : 164 - 173
  • [32] A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis
    Sutton, Caroline
    Brereton, Corinna
    Keogh, Brian
    Mills, Kingston H. G.
    Lavelle, Ed C.
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (07) : 1685 - 1691
  • [33] Cutting Edge: A Critical Functional Role for IL-23 in Psoriasis
    Tonel, Giulia
    Conrad, Curdin
    Laggner, Ute
    Di Meglio, Paola
    Grys, Katarzyna
    McClanahan, Terrill K.
    Blumenschein, Wendy M.
    Qin, Jian-Zhong
    Xin, Hong
    Oldham, Elizabeth
    Kastelein, Robert
    Nickoloff, Brian J.
    Nestle, Frank O.
    [J]. JOURNAL OF IMMUNOLOGY, 2010, 185 (10) : 5688 - 5691
  • [34] IL-17 family cytokines and the expanding diversity of effector T cell lineages
    Weaver, Casey T.
    Hatton, Robin D.
    Mangan, Paul R.
    Harrington, Laurie E.
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2007, 25 : 821 - 852
  • [35] Role of CD4+CD25high+FOXP3+ Regulatory T Cells in Psoriasis
    Yun, Woo-Jin
    Lee, Deok-Woo
    Chang, Sung-Eun
    Yoon, Ghil-Suk
    Huh, Joo-Ryung
    Won, Chong-Hyun
    Lee, Mi-Woo
    Kim, Sung-Eun
    Kim, Beom-Joon
    Moon, Kee-Chan
    Choi, Jee-Ho
    [J]. ANNALS OF DERMATOLOGY, 2010, 22 (04) : 397 - 403
  • [36] Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses
    Zaba, Lisa C.
    Cardinale, Irma
    Gilleaudeau, Patricia
    Sulhvan-Whalen, Mary
    Suarez-Farinas, Mayte
    Fuentes-Duculan, Judilyn
    Novitskaya, Irma
    Khatcherian, Artemis
    Bluth, Mark J.
    Lowes, Michelle A.
    Krueger, James G.
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (13) : 3183 - 3194
  • [37] Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes
    Zaba, Lisa C.
    Suarez-Farinas, Mayte
    Fuentes-Duculan, Judilyn
    Nograles, Kristine E.
    Guttman-Yassky, Emma
    Cardinale, Irma
    Lowes, Michelle A.
    Krueger, James G.
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2009, 124 (05) : 1022 - 1030
  • [38] Psoriasis Is Characterized by Accumulation of Immunostimulatory and Th1/Th17 Cell-Polarizing Myeloid Dendritic Cells
    Zaba, Lisa C.
    Fuentes-Duculan, Judilyn
    Eungdamrong, Narat John
    Abello, Maria Veronica
    Novitskaya, Inna
    Pierson, Katherine C.
    Gonzalez, Juana
    Krueger, James G.
    Lowes, Michelle A.
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2009, 129 (01) : 79 - 88
  • [39] Increased Th17 cells are accompanied by FoxP3+ Treg cell accumulation and correlated with psoriasis disease severity
    Zhang, Li
    Yang, Xue-Qin
    Cheng, Juan
    Hui, Rang-Song
    Gao, Tian-Wen
    [J]. CLINICAL IMMUNOLOGY, 2010, 135 (01) : 108 - 117
  • [40] Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis
    Zheng, Yan
    Danilenko, Dimitry M.
    Valdez, Patricia
    Kasman, Ian
    Eastham-Anderson, Jeffrey
    Wu, Jianfeng
    Ouyang, Wenjun
    [J]. NATURE, 2007, 445 (7128) : 648 - 651