Influence of regulatory T cells on remyelination in the central nervous system
Burns, Alasdair Philip
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The aim of this project is to study whether Regulatory T cells (Treg) influence remyelination following a demyelinating insult of the central nervous system (CNS). Recent studies have shown that biopsies of demyelinated lesions taken from Multiple Sclerosis (MS) patients contain Treg 1. They can also be observed in sites of inflammation within the CNS of mice with Experimental Autoimmune Encephalomyelitis (EAE), a model of MS in which CNS inflammation is induced in animals. Since these cells are found in sites of demyelination and secrete a number of cytokines known to affect oligodendrocyte precursor cell (OPC) and oligodendrocyte cell function (Table 1), it is important to understand if and how they influence repair mechanisms such as remyelination. I have studied the effect that cytokines secreted by Treg have on OPC biology. I have approached this two ways: first by adding conditioned media from in vitro primary cultures of Treg to in vitro primary cultures of OPCs, to study the effects of a full complement of Treg-secreted cytokines on OPCs, and second by choosing the candidate molecule Leukaemia inhibitory factor (LIF), delivered directly to OPCs using nanoparticles. Studies in the past have similarly analysed the effects of single cytokines on OPC behaviour and morphology and conditioned media from other T cell types have been added to microglia. In the future, this work will be extended to studying the effect of Treg and LIF nanoparticles in mouse brain slices ex vivo and in an in vivo mouse model of demyelination.