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

INTRODUCTION

Multiple sclerosis (MS) is an acute demyelinating disease with an autoimmune nature, followed by gradual neurodegeneration and enervating scar formation. Dysregulated immune response is a crucial 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.

RESULTS

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. At the same time, these proteins also 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 contributes to scar formation, and its direct role in MS remains elusive.

DISCUSSION

To develop novel neuroimmunological treatment strategies for MS, the optimal strategy could be the one that causes immune modulation, induces neurogenesis, stimulates remyelination, and prevents excessive scar formation. Therefore, regarding its immunological properties, TGF-β could be an appropriate candidate; 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 role of TGF-β in immunopathogenesis of MS, related clinical and animal studies, and the treatment potential of TGF-β in MS, emphasizing the role of different TGF-β isoforms.