IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation.
IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation.
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DOI：
10.1093/brain/aww113
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发表时间：
2016-07
期刊：
影响因子：
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通讯作者：
Weiner HL
中科院分区：
文献类型：
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作者：
Mayo L;Cunha AP;Madi A;Beynon V;Yang Z;Alvarez JI;Prat A;Sobel RA;Kobzik L;Lassmann H;Quintana FJ;Weiner HL
参见Winger和Zamvil（doi：）对本文的科学评论。 目前的疗法对进展性多发性硬化症（MS）中观察到的慢性CNS炎症的作用有限。马约等人表明，CD 3特异性抗体改善了进行性MS小鼠模型中的疾病。该作用依赖于调节性T细胞的诱导，调节性T细胞通过分泌白细胞介素-10来减弱星形胶质细胞和小胶质细胞的活化。 参见Winger和Zamvil（doi：）对本文的科学评论。 目前的疗法对进展性多发性硬化症（MS）中观察到的慢性CNS炎症的作用有限。马约等人表明，CD 3特异性抗体改善了进行性MS小鼠模型中的疾病。该作用依赖于调节性T细胞的诱导，调节性T细胞通过分泌白细胞介素-10来减弱星形胶质细胞和小胶质细胞的活化。 参见Winger和Zamvil（doi：）对本文的科学评论。 先天免疫系统在慢性中枢神经系统炎症中起着核心作用，慢性中枢神经系统炎症导致多发性硬化症进展形式的神经功能障碍，对此没有有效的治疗方法。粘膜免疫系统是一种独特的致耐受性器官，为诱导调节性T细胞提供了生理途径。在这里，我们报告，鼻腔给药的CD 3特异性抗体改善疾病的进展性多发性硬化症的动物模型。这种作用是IL-10依赖性的，并且通过诱导调节性T细胞介导，所述调节性T细胞与Tr 1调节性细胞具有相似的转录谱并且抑制星形胶质细胞炎症转录程序。治疗导致中枢神经系统中的炎性环境减弱、小胶质细胞活化减少、外周单核细胞募集减少、血脑屏障稳定和神经变性减少。这些发现为治疗进展型多发性硬化症和潜在的其他类型的慢性中枢神经系统炎症提供了一种新的治疗方法。
See Winger and Zamvil (doi: ) for a scientific commentary on this article. Current therapies have limited effect on the chronic CNS inflammation observed in progressive multiple sclerosis (MS). Mayo et al. show that CD3-specific antibody ameliorates disease in a mouse model of progressive MS. The effect is dependent on induction of regulatory T-cells, which attenuate astrocyte and microglia activation via secretion of interleukin-10. See Winger and Zamvil (doi: ) for a scientific commentary on this article. Current therapies have limited effect on the chronic CNS inflammation observed in progressive multiple sclerosis (MS). Mayo et al. show that CD3-specific antibody ameliorates disease in a mouse model of progressive MS. The effect is dependent on induction of regulatory T-cells, which attenuate astrocyte and microglia activation via secretion of interleukin-10. See Winger and Zamvil (doi: ) for a scientific commentary on this article. The innate immune system plays a central role in the chronic central nervous system inflammation that drives neurological disability in progressive forms of multiple sclerosis, for which there are no effective treatments. The mucosal immune system is a unique tolerogenic organ that provides a physiological approach for the induction of regulatory T cells. Here we report that nasal administration of CD3-specific antibody ameliorates disease in a progressive animal model of multiple sclerosis. This effect is IL-10-dependent and is mediated by the induction of regulatory T cells that share a similar transcriptional profile to Tr1 regulatory cells and that suppress the astrocyte inflammatory transcriptional program. Treatment results in an attenuated inflammatory milieu in the central nervous system, decreased microglia activation, reduced recruitment of peripheral monocytes, stabilization of the blood–brain barrier and less neurodegeneration. These findings suggest a new therapeutic approach for the treatment of progressive forms of multiple sclerosis and potentially other types of chronic central nervous system inflammation.