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Nat Med. 2016 May;22(5):516-23. doi: 10.1038/nm.4068. Epub 2016 Mar 28.

Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells.

Author information

1
Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
2
Immunology Program and Infectious Disease Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
3
Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, New York, USA.
4
Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Abstract

Commensal gut bacteria impact the host immune system and can influence disease processes in several organs, including the brain. However, it remains unclear whether the microbiota has an impact on the outcome of acute brain injury. Here we show that antibiotic-induced alterations in the intestinal flora reduce ischemic brain injury in mice, an effect transmissible by fecal transplants. Intestinal dysbiosis alters immune homeostasis in the small intestine, leading to an increase in regulatory T cells and a reduction in interleukin (IL)-17-positive γδ T cells through altered dendritic cell activity. Dysbiosis suppresses trafficking of effector T cells from the gut to the leptomeninges after stroke. Additionally, IL-10 and IL-17 are required for the neuroprotection afforded by intestinal dysbiosis. The findings reveal a previously unrecognized gut-brain axis and an impact of the intestinal flora and meningeal IL-17(+) γδ T cells on ischemic injury.

PMID:
27019327
PMCID:
PMC4860105
DOI:
10.1038/nm.4068
[Indexed for MEDLINE]
Free PMC Article

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