The Effect of Vitamin A Supplementation on FoxP3 and TGF-β Gene Expression in Avonex-Treated Multiple Sclerosis Patients

Abstract

Multiple sclerosis (MS) is an autoinflammatory condition of the central nervous system with impaired T helper (Th)17 and regulatory T cell (Treg) balance that is involved in disease immunopathogenesis. The vitamin A active metabolite, retinoic acid, can re-establish this imbalance through the modulation of gene expression of specific nuclear receptors including Forkhead box P3 (FoxP3). At present, few data exist on the impact of vitamin A supplementation on T cell balance. This study reports the results of a clinical trial, over a 6-month period, of 36 relapsing-remitting MS (RRMS) patients that received vitamin A (25,000 IU retinyl palmitate) or placebo (one capsule of placebo per day). Peripheral blood mononuclear cells were isolated from patients, and the expression of FoxP3 and transforming growth factor (TGF)-β gene expression was measured using real-time PCR at the beginning and end of the study. The results of this study showed that vitamin A upregulated TGF-β and FoxP3 gene expression. Therefore, vitamin A supplementation can be considered as a new approach in MS prevention and treatment.

The T helper type 17/regulatory T cell paradigm in pregnancy

“…Thereby, fluctuations in the numbers of both Th populations seem to be influenced by microRNA clusters, suggesting miRNAs as targets for MS treatment. Additionally, vitamin A supplementation was proposed to up‐regulate Treg markers and may therefore be suitable to reduce disease activity in patients with MS . Other therapeutic interventions shown to reduce IL‐17 and IL‐23 levels, decrease peripheral and central Th17 responses and enhance Treg frequency and IL‐10 production are promising in MS therapy.…”

The Molecular Mechanisms of Vitamin A Deficiency in Multiple Sclerosis

“…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). These findings show that vitamin A plays a key role in MS immunopathogenesis and deficiency of this nutrient can contribute to progression of disease through multiple mechanisms.…”

Nutrition in Multiple Sclerosis: An integrative review of scientific publications from the last 5 years

“…There was also a predominance of studies (19.0%; n= 12) that assessed the role of antioxidant vitamins (A, C and/or E) in the development and/or evolution of MS [9][10][11][12][13][14][15][16][17][18][19][20] and the influence of some natural bioactive compounds, flavonoids and non-flavonoids with antioxidant and/or anti-inflammatory power (12.7%, n= 8), in the disease development, in particular in demyelination 21 control, and consequently, in the progress of symptoms such as muscular weakness and fatigue 22 .…”

“…There were a total of 101 dietary components/nutritional patterns studied because some studies assessed more than one of these components. 56 ; Jelinek et al 52 ; Koriem 57 ; Malli et al 31 ; Masullo et al 13 ; Peterlik 58 ; Polachini et al 16 ; Romero et al 59 ; Schmitz et al 18 ; Shiri-Shahsavar et al 19 ; Torkildsen et al 20 63 ; Hoare et al 62 ; Mauriz et al 14 ; Nieto et al 15 ; Pantzaris et al 61 ; Rezapour-Firouzi et al 28 ; Rezapour-Firouzi et al 30 ; Schmitz et al 18 ; Shiri-Shahsavar et al 19 ; Timmermans et al 60 ; Weiland et al 43 Antioxidant Vitamins 12 19.0 Dorosty-Motlagh et al 9 ; Geldern; Mowry 10 ; Honarvar et al 11 ; Loken-Amsrud 12 ; Masullo et al 13 ; Mauriz et al 14 ; Nieto et al 15 ; Polachini et al 16 ; Saboor-Yaraghi et al 17 ; Schmitz et al 18 ; Shiri-Shahsavar et al 19 ; Torkildsen et al 20 Bioactive compounds 8 12. Hagan et al 35 ; Jelinek et al 36 ; Oliveira et al 37 ; Wens et al 38 .…”