Mondal Susanta, Dasarathi Sridevi, Pahan Kalipada
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
J Clin Cell Immunol. 2017 Feb;8(1). doi: 10.4172/2155-9899.1000488. Epub 2017 Jan 31.
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 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.
多发性硬化症(MS)是中枢神经系统(CNS)最常见的自身免疫性脱髓鞘疾病。在此,我们探索了一种调味成分三苯甲酸甘油酯(GTB)的新用途,即通过转化生长因子-β(TGF-β)改善实验性变应性脑脊髓炎(EAE)的疾病进程,EAE是MS的动物模型。口服GTB可抑制受体小鼠中过继转移的复发缓解型(RR)EAE的临床症状,并抑制供体小鼠中致脑炎性T细胞的产生。GTB还减轻了PLP-TCR转基因小鼠中RR-EAE的临床症状以及雄性C57/BL6小鼠中慢性EAE的临床症状。相应地,GTB还抑制了血管周围套叠,维持了血脑屏障和血脊髓屏障的完整性,抑制了炎症,并阻止了EAE小鼠中枢神经系统中的脱髓鞘。有趣的是,GTB治疗上调了TGF-β,并使脾细胞以及EAE小鼠中的调节性T细胞(Tregs)增多。用中和抗体阻断TGF-β消除了GTB介导的Tregs富集和对EAE的保护作用。这些结果表明,口服GTB可能被视为MS患者的一种可能治疗方法。