The MS Remyelinating Drug Bexarotene (an RXR Agonist) Promotes Induction of Human Tregs and Suppresses Th17 Differentiation In Vitro
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 r...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.712241/full |
| _version_ | 1818433694561468416 |
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| author | Christopher M. Gaunt Daniel B. Rainbow Daniel B. Rainbow Ruairi J. Mackenzie Lorna B. Jarvis Hani S. Mousa Nicholas Cunniffe Zoya Georgieva J. William Brown Alasdair J. Coles Joanne L. Jones |
| author_facet | Christopher M. Gaunt Daniel B. Rainbow Daniel B. Rainbow Ruairi J. Mackenzie Lorna B. Jarvis Hani S. Mousa Nicholas Cunniffe Zoya Georgieva J. William Brown Alasdair J. Coles Joanne L. Jones |
| author_sort | Christopher M. Gaunt |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T16:25:10Z |
| format | Article |
| id | doaj.art-9f412517dd1e4c2d980a2b0118b6c987 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T16:25:10Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9f412517dd1e4c2d980a2b0118b6c9872022-12-21T22:54:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-08-011210.3389/fimmu.2021.712241712241The MS Remyelinating Drug Bexarotene (an RXR Agonist) Promotes Induction of Human Tregs and Suppresses Th17 Differentiation In VitroChristopher M. Gaunt0Daniel B. Rainbow1Daniel B. Rainbow2Ruairi J. Mackenzie3Lorna B. Jarvis4Hani S. Mousa5Nicholas Cunniffe6Zoya Georgieva7J. William Brown8Alasdair J. Coles9Joanne L. Jones10Department of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDepartment of Genetics, Medical Science Division, University of Oxford, Oxford, United KingdomDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.712241/fullT cellsTh17 & Tregs cellsmultiple sclerosisautoimmunityretinoid X receptor (RXR)retinoids |
| spellingShingle | Christopher M. Gaunt Daniel B. Rainbow Daniel B. Rainbow Ruairi J. Mackenzie Lorna B. Jarvis Hani S. Mousa Nicholas Cunniffe Zoya Georgieva J. William Brown Alasdair J. Coles Joanne L. Jones The MS Remyelinating Drug Bexarotene (an RXR Agonist) Promotes Induction of Human Tregs and Suppresses Th17 Differentiation In Vitro Frontiers in Immunology T cells Th17 & Tregs cells multiple sclerosis autoimmunity retinoid X receptor (RXR) retinoids |
| title | The MS Remyelinating Drug Bexarotene (an RXR Agonist) Promotes Induction of Human Tregs and Suppresses Th17 Differentiation In Vitro |
| title_full | The MS Remyelinating Drug Bexarotene (an RXR Agonist) Promotes Induction of Human Tregs and Suppresses Th17 Differentiation In Vitro |
| title_fullStr | The MS Remyelinating Drug Bexarotene (an RXR Agonist) Promotes Induction of Human Tregs and Suppresses Th17 Differentiation In Vitro |
| title_full_unstemmed | The MS Remyelinating Drug Bexarotene (an RXR Agonist) Promotes Induction of Human Tregs and Suppresses Th17 Differentiation In Vitro |
| title_short | The MS Remyelinating Drug Bexarotene (an RXR Agonist) Promotes Induction of Human Tregs and Suppresses Th17 Differentiation In Vitro |
| title_sort | ms remyelinating drug bexarotene an rxr agonist promotes induction of human tregs and suppresses th17 differentiation in vitro |
| topic | T cells Th17 & Tregs cells multiple sclerosis autoimmunity retinoid X receptor (RXR) retinoids |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.712241/full |
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