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The MS Remyelinating Drug Bexarotene (an RXR Agonist) Promotes Induction of Human Tregs and Suppresses Th17 Differentiation In Vitro.

Published version
Peer-reviewed

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Article

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Authors

Gaunt, Christopher M 
Rainbow, Daniel B 
Mackenzie, Ruairi J 
Jarvis, Lorna B 
Mousa, Hani S 

Abstract

The retinoid X receptor agonist bexarotene promotes remyelination in patients with multiple sclerosis. Murine studies have also demonstrated that RXR agonists have anti-inflammatory effects by enhancing the ability of all-trans-retinoic acid (atRA) to promote T-regulatory cell (Treg) induction and reduce Th17 differentiation in vitro. By stimulating human naïve CD4 T-cells in the presence of Treg or Th17 skewing cytokines, we show that bexarotene also tips the human Treg/Th17 axis in favor of Treg induction, but unlike murine cells this occurs independently of atRA and retinoic acid receptor signaling. Tregs induced in the presence of bexarotene express canonical markers of T-regulation and are functionally suppressive in vitro. Circulating Treg numbers did not increase in the blood of trial patients receiving bexarotene; we believe this is because Treg induction is likely to occur within tissues. These findings lend support to developing RXR agonists as treatments of autoimmune diseases, in particular multiple sclerosis.

Description

Funder: Biotechnology and Biological Sciences Research Council


Funder: Wellcome Trust


Funder: NIHR Cambridge Biomedical Research Centre

Keywords

T cells, Multiple sclerosis, Autoimmunity, Retinoids, Retinoid X Receptor (Rxr), Th17 & Tregs Cells

Journal Title

Frontiers in immunology

Conference Name

Journal ISSN

1664-3224

Volume Title

12

Publisher