期刊
BRAIN
卷 139, 期 -, 页码 1939-1957出版社
OXFORD UNIV PRESS
DOI: 10.1093/brain/aww113
关键词
astrocyte; neuroinflammation; multiple sclerosis; T-lymphocytes; interleukin 10
资金
- NIH [R01AI043458, P01NS076410]
- National Multiple Sclerosis Society [FG1941A1/2]
- Harry Weaver Award from National Multiple Sclerosis Society
- Austrian Science Foundation (FWF) [P 27744-B24]
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.
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