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Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis
被引:191
作者:

Roehn, Till A.
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机构: Cytos Biotechnol AG, CH-8952 Schlieren, Switzerland

Jennings, Gary T.
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机构: Cytos Biotechnol AG, CH-8952 Schlieren, Switzerland

Hernandez, Marcela
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机构: Cytos Biotechnol AG, CH-8952 Schlieren, Switzerland

Grest, Paula
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机构: Cytos Biotechnol AG, CH-8952 Schlieren, Switzerland

Beck, Markus
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机构: Cytos Biotechnol AG, CH-8952 Schlieren, Switzerland

Zou, Yu
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机构: Cytos Biotechnol AG, CH-8952 Schlieren, Switzerland

Kopf, Manfred
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机构: Cytos Biotechnol AG, CH-8952 Schlieren, Switzerland

Bachmann, Martin F.
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机构: Cytos Biotechnol AG, CH-8952 Schlieren, Switzerland
机构:
[1] Cytos Biotechnol AG, CH-8952 Schlieren, Switzerland
[2] Univ Zurich, Vetsuisse Fac, Inst Vet Pathol, CH-8006 Zurich, Switzerland
[3] ETH, Inst Biomed Res, Zurich, Switzerland
关键词:
autoimmune diseases;
IL-17;
vaccination;
virus-like particles;
D O I:
10.1002/eji.200636658
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Interleukin 17 is a T cell-derived cytokine that induces the release of pro-inflammatory mediators in a wide range of cell types. Recently, a subset of IL-17-producing T helper cells (Th17) distinct from Th1 and Th2 cells has been described, which constitutes a new T cell polarization state. Aberrant Th17 responses and overexpression of IL-17 have been implicated in a number of autoimmune disorders including rheumatoid arthritis and multiple sclerosis. Molecules blocking IL-17 such as IL-17-specific monoclonal antibodies have proved to be effective in ameliorating disease in animal models. Hitherto, active immunization targeting IL-17 is an untried approach. Herein we explore the potential of neutralizing IL-17 by active immunization using virus-like particles conjugated with recombinant IL-17 (IL-17-VLP). Immunization with IL-17-VLP induced high levels of anti-IL-17 antibodies thereby overcoming natural tolerance, even in the absence of added adjuvant. Mice immunized with IL-17-VLP had lower incidence of disease, slower progression to disease and reduced scores of disease severity in both collagen-induced arthritis and experimental autoimmune encephalomyelitis. Active immunization against IL-17 therefore represents a novel therapeutic approach for the treatment of chronic inflammatory diseases.
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页码:2857 / 2867
页数:11
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