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
相关论文
共 44 条
[11]   Mutilation of RNA phage Qβ virus-like particles:: from icosahedrons to rods [J].
Cielens, I ;
Ose, V ;
Petrovskis, I ;
Strelnikova, A ;
Renhofa, R ;
Kozlovska, T ;
Pumpens, P .
FEBS LETTERS, 2000, 482 (03) :261-264
[12]   Collagen-induced arthritis development requires αβ T cells but not γδ T cells:: studies with T cell-deficient (TCR mutant) mice [J].
Corthay, A ;
Johansson, Å ;
Vestberg, M ;
Holmdahl, R .
INTERNATIONAL IMMUNOLOGY, 1999, 11 (07) :1065-1073
[13]   Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain [J].
Cua, DJ ;
Sherlock, J ;
Chen, Y ;
Murphy, CA ;
Joyce, B ;
Seymour, B ;
Lucian, L ;
To, W ;
Kwan, S ;
Churakova, T ;
Zurawski, S ;
Wiekowski, M ;
Lira, SA ;
Gorman, D ;
Kastelein, RA ;
Sedgwick, JD .
NATURE, 2003, 421 (6924) :744-748
[14]   IL-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide-induced airway neutrophilia: IL-15 as a possible trigger [J].
Ferretti, S ;
Bonneau, O ;
Dubois, GR ;
Jones, CE ;
Trifilieff, A .
JOURNAL OF IMMUNOLOGY, 2003, 170 (04) :2106-2112
[15]   Cytokine inhibitors in the treatment of rheumatoid arthritis [J].
Gabay, C .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2002, 2 (02) :135-149
[16]   Expanding the effector CD4 T-cell repertoire: the Th17 lineage [J].
Harrington, Laurie E. ;
Mangan, Paul R. ;
Weaver, Casey T. .
CURRENT OPINION IN IMMUNOLOGY, 2006, 18 (03) :349-356
[17]   Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis [J].
Hofstetter, HH ;
Ibrahim, SM ;
Koczan, D ;
Kruse, N ;
Weishaupt, A ;
Toyka, KV ;
Gold, R .
CELLULAR IMMUNOLOGY, 2005, 237 (02) :123-130
[18]   A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses [J].
Jegerlehner, A ;
Tissot, A ;
Lechner, F ;
Sebbel, P ;
Erdmann, I ;
Kündig, T ;
Bächi, T ;
Storni, T ;
Jennings, G ;
Pumpens, P ;
Renner, WA ;
Bachmann, MF .
VACCINE, 2002, 20 (25-26) :3104-3112
[19]   Interleukin-17 family members and inflammation [J].
Kolls, JK ;
Lindén, A .
IMMUNITY, 2004, 21 (04) :467-476
[20]   IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis [J].
Komiyama, Yutaka ;
Nakae, Susumu ;
Matsuki, Taizo ;
Nambu, Aya ;
Ishigame, Harumichi ;
Kakuta, Shigeru ;
Sudo, Katsuko ;
Iwakura, Yoichiro .
JOURNAL OF IMMUNOLOGY, 2006, 177 (01) :566-573