Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis

被引:191
作者
Roehn, Till A.
Jennings, Gary T.
Hernandez, Marcela
Grest, Paula
Beck, Markus
Zou, Yu
Kopf, Manfred
Bachmann, Martin F.
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.
引用
收藏
页码:2857 / 2867
页数:11
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