Impact of Vitamin A Supplementation on RAR Gene Expression in Multiple Sclerosis Patients

Abstract

Vitamin A and its derivatives have been shown to modulate the immune system via retinoic acid receptor (RAR). This study explored the impact of retinyl palmitate supplementation on RAR subtype gene expression in peripheral blood mononuclear cells (PBMCs) in multiple sclerosis (MS) patients. The study designed as a double-blind randomized clinical trial in which relapsing remitting multiple sclerosis patients were evaluated. Both groups received one capsule 50,000 IU vitamin D3 per 2 weeks and one intramuscular injection interferon beta-1a per week. The intervention group received one 25,000 IU retinyl palmitate capsule daily for 6 months and the placebo group received one placebo capsule daily. The PBMCs were isolated from participants and the expression level changes of RAR-α and RAR-γ genes were determined by real-time PCR. After supplementation, in the intervention group, the RAR-α gene expression level was significantly decreased compared to the placebo group (p = 0.03); however, the expression of RAR-γ gene did not significantly change (p = 0.10). These results show that vitamin A supplementation can significantly downregulate the expression of RAR-α gene in PBMCs of MS patients that suggest the presence of in vivo regulatory mechanisms for the action of vitamin A on the immune system.

Retinoic Acid, Leaky Gut, and Autoimmune Diseases

“…Indeed, vitamin A has been proposed to derive intrinsic immunoregulation within the CNS tissue under the MS condition [ 99 ]. RA is intrinsically produced by the reactive astrocytes that exhibit upregulated RALDH2 expression.…”

The Molecular Mechanisms of Vitamin A Deficiency in Multiple Sclerosis

“…In this regard, we previously reported that vitamin A supplementation (25,000 IU/day for 6 months) led to lower proliferation of myelin oligodendrocyte glycoprotein-reactive lymphocytes in MS patients ). Our team found that vitamin A supplementation results in downregulation of RARα and RARγ in PBMCs of MS patients (Bitarafan et al 2013). Furthermore, vitamin A supplementation significantly reduces IL-17 levels and inhibits gene expression of RORγt , reciprocally promoting TGF-β production and inducing FoxP3 expression in patients with MS (Saboor-Yaraghi et al 2015).…”

The influence of retinoic acid on the human oligodendrocyte precursor cells by RNA-sequencing

“…Previously, it was shown to inhibit oligodendrocyte maturation during CNS myelination [32] , and known as a negative regulator through an RAR-dependent mechanism in the PNS [33] , but the down-regulators involved in this inhibitory signaling were not determined. It has been demonstrated that RARα and RARγ were down-regulated in peripheral blood mononuclear cells (PBMC) from MS patients who take dietary vitamin A daily [34] . The analyses of the biology of RA have focused mostly on its interaction with the immune system as shown by the large number of clinical studies using RA as a supplement [35] .…”