Dataset Information


Breaking immune tolerance by targeting Foxp3(+) regulatory T cells mitigates Alzheimer's disease pathology.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder in which chronic neuroinflammation contributes to disease escalation. Nevertheless, while immunosuppressive drugs have repeatedly failed in treating this disease, recruitment of myeloid cells to the CNS was shown to play a reparative role in animal models. Here we show, using the 5XFAD AD mouse model, that transient depletion of Foxp3(+) regulatory T cells (Tregs), or pharmacological inhibition of their activity, is followed by amyloid-? plaque clearance, mitigation of the neuroinflammatory response and reversal of cognitive decline. We further show that transient Treg depletion affects the brain's choroid plexus, a selective gateway for immune cell trafficking to the CNS, and is associated with subsequent recruitment of immunoregulatory cells, including monocyte-derived macrophages and Tregs, to cerebral sites of plaque pathology. Our findings suggest targeting Treg-mediated systemic immunosuppression for treating AD.


PROVIDER: S-EPMC4557123 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

2019-01-01 | S-EPMC6704256 | BioStudies
2015-01-01 | S-EPMC4697843 | BioStudies
2020-01-01 | S-EPMC7507727 | BioStudies
2018-01-01 | S-EPMC6319620 | BioStudies
2011-01-01 | S-EPMC3038736 | BioStudies
2010-01-01 | S-EPMC2944006 | BioStudies
2020-01-01 | S-EPMC7224338 | BioStudies
2011-01-01 | S-EPMC3257046 | BioStudies
2016-01-01 | S-EPMC4839340 | BioStudies
2012-01-01 | S-EPMC3690568 | BioStudies