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

Autor:	Gaunt CM; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom., Rainbow DB; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.; Department of Genetics, Medical Science Division, University of Oxford, Oxford, United Kingdom., Mackenzie RJ; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom., Jarvis LB; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom., Mousa HS; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom., Cunniffe N; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom., Georgieva Z; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom., Brown JW; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom., Coles AJ; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom., Jones JL; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Aug 10; Vol. 12, pp. 712241. Date of Electronic Publication: 2021 Aug 10 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.712241
Abstrakt:	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 ( at RA) 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 at RA 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Gaunt, Rainbow, Mackenzie, Jarvis, Mousa, Cunniffe, Georgieva, Brown, Coles and Jones.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu