Glyceryl Tribenzoate: A Flavoring Ingredient, Inhibits the Adoptive Transfer of Experimental Allergic Encephalomyelitis via TGF-β: Implications for Multiple Sclerosis Therapy.

Susanta Mondal,Sridevi Dasarathi,Kalipada Pahan

doi:10.4172/2155-9899.1000488

Abstract

Multiple sclerosis (MS) is the most common autoimmune demyelinating disease of the central nervous system (CNS). Here, we have explored a novel use of glyceryl tribenzoate (GTB), a flavoring ingredient, in ameliorating the disease process of experimental allergic encephalomyelitis (EAE), an animal model of MS, via TGF-β. Oral feeding of GTB suppressed clinical symptoms of adoptively-transferred relapsing-remitting (RR) EAE in recipient mice and suppressed the generation of encephalitogenic T cells in donor mice. GTB also attenuated clinical symptoms of RR-EAE in PLP-TCR transgenic mice and chronic EAE in male C57/BL6 mice. Accordingly, GTB also suppressed perivascular cuffing, preserved the integrity of blood-brain barrier and blood-spinal cord barrier, inhibited inflammation, and stopped demyelination in the CNS of EAE mice. Interestingly, GTB treatment upregulated TGF-β and enriched regulatory T cells (Tregs) in splenocytes as well as in vivo in EAE mice. Blocking TGF-β by neutralizing antibodies abrogated GTB-mediated enrichment of Tregs and protection of EAE. These results suggest that oral GTB may be considered as a possible therapy for MS patients.

Highlights

Tissue-specific autoimmunity can be inhibited by subpopulations of CD4+ cells, termed as regulatory T cells (Tregs) [1,2]
The presence of forkhead box protein 3 (Foxp3) is an important feature of Tregs and these cells often characterized by the presence of Foxp3 and Foxp3+ CD4+CD25+ T cells [1,3]
Treatment of EAE mice by Glyceryl tribenzoate (GTB) markedly attenuated the entry of infra-red dye into the spinal cord and different parts of the brain (Figures 3B–3D; compare lane 3 with lane 2). These results suggest that GTB treatment preserves the integrity of blood-brain barrier (BBB) and blood-spinal cord barrier (BSB) in EAE mice

Summary

Introduction

Tissue-specific autoimmunity can be inhibited by subpopulations of CD4+ cells, termed as regulatory T cells (Tregs) [1,2] These cells are capable of suppressing activation and proliferation of self-reactive T cells and thereby inhibition of immune response of selfreactive T cells against self-antigens [1,2]. During autoimmune insults, the immune system is altered, resulting in a decrease in the function and the number of Tregs. This dysfunction and/or loss of Tregs lead to proliferation of self-reactive T cells and subsequent autoimmune attack. TGF-β, a multifunctional cytokine, is known to inhibit immune responses is through promoting the generation of Tregs by inducing the expression of Foxp. Suggest that GTB may be used to control autoimmune pathologies in MS via upregulation/ maintenance of TGF-β

Materials and Methods

Results

Discussion