AUTHOR=Gaunt Christopher M. , Rainbow Daniel B. , Mackenzie Ruairi J. , Jarvis Lorna B. , Mousa Hani S. , Cunniffe Nicholas , Georgieva Zoya , Brown J. William , Coles Alasdair J. , Jones Joanne L. 

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.712241

DOI=10.3389/fimmu.2021.712241

ISSN=1664-3224

ABSTRACT=<p>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 (<italic>at</italic>RA) to promote T-regulatory cell (Treg) induction and reduce Th17 differentiation <italic>in vitro.</italic> 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 <italic>at</italic>RA and retinoic acid receptor signaling. Tregs induced in the presence of bexarotene express canonical markers of T-regulation and are functionally suppressive <italic>in vitro.</italic> 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.</p>