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

Lior Mayo, Andre Pires Da Cunha, Asaf Madi, Vanessa Beynon, Zhiping Yang, Jorge I. Alvarez, Alexandre Prat, Raymond A. Sobel, Lester Kobzik, Hans Lassmann, Francisco J. Quintana, Howard L. Weiner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

See Winger and Zamvil (doi:10.1093/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.

Original languageEnglish
Pages (from-to)1939-1957
Number of pages19
JournalBrain
Volume139
Issue number7
DOIs
StatePublished - 1 Jul 2016

Funding

FundersFunder number
Austrian Science Foundation
National Institutes of HealthFG1941A1/2
National Institute of Allergy and Infectious DiseasesR01AI043458, R01AI126880
National Institute of Neurological Disorders and StrokeP01NS076410
National Multiple Sclerosis Society
Austrian Science FundP 27744-B24

    Keywords

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

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