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Brain. 2016 Jul;139(Pt 7):1939-57. doi: 10.1093/brain/aww113. Epub 2016 May 31.

IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation.

Author information

1
1 Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA 2 Cell Research and Immunology Department, Sagol School of Neuroscience, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 699788, Israel.
2
1 Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
3
3 Evergrande Center for Immunologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA.
4
4 Environmental Health Department, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
5
5 Neuroimmunology Research Lab, CRCHUM, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada 6 Pathobiology Department, University of Pennsylvania, Philadelphia, PA 19104, USA.
6
5 Neuroimmunology Research Lab, CRCHUM, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
7
7 Stanford University School of Medicine, Stanford, USA.
8
8 Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Wien, Austria.
9
1 Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA hweiner@rics.bwh.harvard.edu.

Abstract

SEE WINGER AND ZAMVIL DOI101093/BRAIN/AWW121 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.

KEYWORDS:

T-lymphocytes; astrocyte; interleukin 10; multiple sclerosis; neuroinflammation

PMID:
27246324
PMCID:
PMC4939696
DOI:
10.1093/brain/aww113
[Indexed for MEDLINE]
Free PMC Article

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