Breaking immune tolerance by targeting Foxp3+ regulatory T cells mitigates Alzheimer’s disease pathology

Kuti Baruch (), Neta Rosenzweig, Alexander Kertser, Aleksandra Deczkowska, Alaa Mohammad Sharif, Amit Spinrad, Afroditi Tsitsou-Kampeli, Ayelet Sarel, Liora Cahalon and Michal Schwartz ()
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Kuti Baruch: Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel
Neta Rosenzweig: Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel
Alexander Kertser: Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel
Aleksandra Deczkowska: Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel
Alaa Mohammad Sharif: Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel
Amit Spinrad: Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel
Afroditi Tsitsou-Kampeli: Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel
Ayelet Sarel: Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel
Liora Cahalon: Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel
Michal Schwartz: Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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-β 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.

Date: 2015
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DOI: 10.1038/ncomms8967

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