T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis

被引：432

作者：

Axtell, Robert C. ^{[1
]}

de Jong, Brigit A. ^{[1
,2
,3
]}

Boniface, Katia ^{[4
,5
]}

van der Voort, Laura F. ^{[3
]}

Bhat, Roopa ^{[1
]}

De Sarno, Patrizia ^{[6
]}

Naves, Rodrigo ^{[7
]}

Han, May ^{[1
]}

Zhong, Franklin ^{[1
]}

Castellanos, Jim G. ^{[1
]}

Mair, Robert ^{[1
]}

Christakos, Athena ^{[1
]}

Kolkowitz, Ilan ^{[1
]}

Katz, Liat ^{[1
]}

Killestein, Joep ^{[3
]}

Polman, Chris H. ^{[3
]}

Malefyt, Rene de Waal ^{[4
,5
]}

Steinman, Lawrence ^{[1
]}

Raman, Chander ^{[7
]}

机构：

[1] Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

[2] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, NL-6525 ED Nijmegen, Netherlands

[3] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands

[4] Schering Plough Biopharma, Palo Alto, CA USA

[5] DNAX Res Inst Mol & Cellular Biol Inc, Dept Immunol, Palo Alto, CA 94304 USA

[6] Univ Alabama, Dept Psychiat & Behav Neurobiol, Birmingham, CA USA

[7] Univ Alabama, Dept Med, Birmingham, CA USA

来源：

NATURE MEDICINE | 2010年 / 16卷 / 04期

基金：

美国国家卫生研究院;

关键词：

AUTOIMMUNE INFLAMMATION; NEUROMYELITIS-OPTICA; IFN-ALPHA; TGF-BETA; GAMMA; DIFFERENTIATION; THERAPY; IL-23; INHIBITION; ACTIVATION;

D O I：

10.1038/nm.2110

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Interferon-beta (IFN-beta) is the major treatment for multiple sclerosis. However, this treatment is not always effective. Here we have found congruence in outcome between responses to IFN-beta in experimental autoimmune encephalomyelitis (EAE) and relapsing-remitting multiple sclerosis (RRMS). IFN-beta was effective in reducing EAE symptoms induced by T helper type 1 (T(H)1) cells but exacerbated disease induced by T(H)17 cells. Effective treatment in T(H)1-induced EAE correlated with increased interleukin-10 (IL-10) production by splenocytes. In T(H)17-induced disease, the amount of IL-10 was unaltered by treatment, although, unexpectedly, IFN-beta treatment still reduced IL-17 production without benefit. Both inhibition of IL-17 and induction of IL-10 depended on IFN-gamma. In the absence of IFN-gamma signaling, IFN-beta therapy was ineffective in EAE. In RRMS patients, IFN-beta nonresponders had higher IL-17F concentrations in serum compared to responders. Nonresponders had worse disease with more steroid usage and more relapses than did responders. Hence, IFN-beta is proinflammatory in T(H)17-induced EAE. Moreover, a high IL-17F concentration in the serum of people with RRMS is associated with nonresponsiveness to therapy with IFN-beta.

引用

页码：406 / U21

页数：8

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