The MS Remyelinating Drug Bexarotene (an RXR Agonist) Promotes Induction of Human Tregs and Suppresses Th17 Differentiation In Vitro
- Resource Type
- Authors
- Lorna B. Jarvis; Daniel B. Rainbow; Zoya Georgieva; Nicholas James Cunniffe; Alasdair Coles; Ruairi J Mackenzie; Hani S Mousa; Christopher M Gaunt; J William L Brown; Joanne L Jones
- Source
- Frontiers in Immunology, Vol 12 (2021)
Frontiers in Immunology
- Subject
- CD4-Positive T-Lymphocytes
Th17 & Tregs cells
Cell
medicine.disease_cause
multiple sclerosis
T-Lymphocytes, Regulatory
Autoimmunity
Immunology and Allergy
Alitretinoin
Cells, Cultured
Original Research
Bexarotene
Clinical Trials as Topic
Lymphopoiesis
autoimmunity
hemic and immune systems
Forkhead Transcription Factors
Middle Aged
medicine.anatomical_structure
retinoid X receptor (RXR)
Fatty Acids, Unsaturated
Female
medicine.drug
Agonist
Adult
retinoids
Tetrahydronaphthalenes
medicine.drug_class
Immunology
T cells
chemical and pharmacologic phenomena
Retinoid X receptor
medicine
Humans
Remyelination
business.industry
Multiple sclerosis
FOS: Clinical medicine
RC581-607
medicine.disease
Retinoic acid receptor
Retinoid X Receptors
Cancer research
Leukocytes, Mononuclear
Th17 Cells
Immunologic diseases. Allergy
business
- Language
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.