TGF‐β regulation of encephalitogenic and regulatory T cells in multiple sclerosis

Abstract

Transforming growth factor-beta (TGF-β) is a pleiotrophic cytokine that has been shown to influence the differentiation and function of T cells. As such, the role that TGF-β plays in immune-mediated disease, such as multiple sclerosis (MS), has become a major area of investigation since CD4 T cells appear to be a major mediator of the autoimmunity. This review analysis the literature on the role that TGF-β plays in the generation and regulation of encephalitogenic T cells in experimental autoimmune encephalomyelitis, an animal model of MS, as well as T cells of MS patients. Since TGF-β plays a major role in the development and function of CD4 regulatory T cells, which are defective in MS patients, recent studies have found potential mechanisms to explain the basis for these regulatory T cell defects to establish a foundation for potentially modulating TGF-β signaling to restore normal T cell function in MS patients.

The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives

“…Since MS is an autoimmune disorder characterized by neuronal damage, demyelination, and chronic inflammation, it seems that cytokines are significant inflammation mediators. In particular, IL-27 and TGFβ modify inflammation and can be secreted directly at inflammatory sites in the CNS during MS [16,24]. In agreement with this paper's findings, Tang et al [7] explored the role of IL-27 in MS patients and reported that plasma and mRNA expression levels of IL-27 had declined in MS patients.…”

“…Furthermore, more studies reported that IL-27 could quell inflammation state through prohibiting the function and the differentiation of Th17 cells, particularly repression to the secretion of IL-17A via JAK1-STAT1 [36], followed by ameliorated clinical symptoms and development of MS disease [11,19,35]. Various studies have illustrated the role of TGF-β1 in inciting the production of IL-10 [32,37,38], and also, it has become elucidated that TGF-β1 can trigger IL-10 through Smad4 pathway [16]. Following the same issue, TGF-β1 could repress the differentiation of naive CD4+ T cells into pathogenic Th17 ones and down-regulate the mRNA expression of IL-17 due to the immunosuppressive traits [39][40][41].…”

“…Nevertheless, it is notable that TGF-β1 promotes differentiation of naïve CD4+ T cells into Foxp3 + Tregs through signal STAT5, thereby increasing the expression of antiinflammatory cytokines like IL-10. Additionally, TGF-β1 plays a preventative role in terms of the entrance of sensitized T cells into the CNS and consequently quells the production of proinflammatory cytokines [14,16,17]. Naïve CD4+ T cells can nonetheless be converted into immature Th17 in the presence of IL-6 and via signal STAT3.…”

miR-320 and Inflammation Regulation in Experimental Autoimmune Encephalomyelitis Through Interference With Tumor Growth Factor-β Signaling Pathway

“…TGF-β1 contributes to the protection of our body against the auto-reactive T cells by increasing the differentiation of CD4+ T cells into Treg cells. TGF-β also prevents differentiation of CD4+ T cells towards Th1, which leads to a decrease in IFN-γ production and induction of EAE [29]. TGF-β1 has various effects, especially protective one in the context of MS/ EAE.…”

Regulatory T Lymphocytes (Treg): Modulation and Clinical Application

“…The use of TGF-β may be an alternative aid in the treatment of multiple sclerosis, since Treg and effector T cells are defective. The causes of multiple sclerosis are still unknown, but the immune system plays a central role in the development of the disease [98,99].…”