Transforming growth factor β (TGF-β) pathway in immunopathogenesis of multiple sclerosis (MS); molecular approaches

Abstract

AbstractMultiple sclerosis (MS) is an acute demyelinating disease with an autoimmune nature, followed by gradual neurodegeneration and enervating scar formation. Dysregulated immune response is an important dilemma contributing to the pathogenesis of MS. The role of chemokines and cytokines, such as transforming growth factor-β (TGF-β), have been recently highlighted regarding their altered expressions in MS. TGF-β has three isoforms, TGF-β1, TGF-β2, and TGF-β3, that are structurally similar; however, they can show different functions. All three isoforms are known to induce immune tolerance by modifying Foxp3+regulatory T cells. Nevertheless, there are controversial reports concerning the role of TGF-β1 and 2 in the progression of scar formation in MS, while these proteins are also known to improve oligodendrocyte differentiation and have shown neuroprotective behavior, two cellular processes that suppress the pathogenesis of MS. TGF-β3 shares the same properties but is less likely to contribute to scar formation and its direct role in MS remains elusive. To develop novel neuroimmunological treatment strategies for MS, the optimal strategy could be the one that causes immune suppression, induces neurogenesis, stimulates remyelination, and prevents excessive scar formation. Therefore, regarding its immunological properties, TGF-β could be an appropriate candidate for this; however, contradictory results of previous studies have questioned its role and therapeutic potential in MS. In this review article, we provide an overview of the immunopathogenesis of MS, the role of TGF-β in this process, related clinical and animal studies, and the treatment potential of TGF-β in MS by emphasizing the role of different TGF-β isoforms.