Project R-13316

Regulatory T cells in multiple sclerosis: from methylation to (re)myelination (Research)

Multiple sclerosis (MS) is an autoimmune-induced demyelinating disease of the central nervous system (CNS). Focal demyelination, the primary hallmark of MS, results in neurodegeneration due to oligodendrocyte death and loss of axonal function. In MS, regulatory T cells (Tregs), which possess regenerative functions, are compromised. In homeostatic conditions, Tregs promote remyelination through the secretion of factors such as nephroblastoma overexpressed (NOV/CCN3), leukaemia inhibitory factor (LIF) and transforming growth factor β (TGF-β). However, it is thought that in MS, epigenetic imprinting of Tregs is altered during the course of the disease, causing impaired Treg function. Targeting the remyelination pathway of Tregs may have ground-breaking implications for progressive MS (pMS) patients, who currently have no approved treatments that target repair. Furthermore, Tregs are required for successful remyelination to occur, thus designing a Treg based remyelination therapy may help to alleviate the remyelination block observed in pMS and prevent further disease progression. Accordingly, I aim to determine which Treg-associated remyelination inducing genes have an altered epigenetic imprinting in MS patients and whether epigenetic editing of those genes is able to promote remyelination through the adoptive transfer of epigenetically edited Tregs into models of MS. Ultimately, I aim to investigate a potential cell-based autologous Treg therapy for remyelination in pMS.

01 November 2022 - 31 October 2026