Impaired Control of T cell–B cell interactions by follicular regulatory T cells in Multiple Sclerosis

Multiple sclerosis (MS) is a complex condition, characterised by an aberrant immune response which triggers the destruction of myelin in the central nervous system. Clinical manifestations are of neurodegenerative nature, but it is an autoimmune condition driven by pathogenetic T and B cell responses. Follicular regulatory T cells (Tfr) are essential for controlling T cell-B cell interactions, and growing evidence suggests that their dysfunction is associated with several autoimmune conditions. Interestingly, Tfr function is impaired in people with MS, but the underlying cellular and molecular mechanisms and their contribution to disease pathogenesis and progression remains to be addressed.This project aims at identifying the mechanisms responsible for the impaired function of Tfrs, contributing to exacerbated T cell-B cell interactions in people living with MS. I will dissect the extent and nature of Tfr dysfunctional phenotype, to identify disease modified signatures. Using this information, I will then modulate these targets and evaluate the impact on Tfr cell function. Ultimately, the use of an animal model of MS will allow me to ascertain the organismal impact of modulating the impaired pathways found in Tfr cells of people with MS, in disease recovery and progression.Collectively, the results of this work will help identify the mechanisms underlying Tfr dysfunction, responsible for exacerbated T cell-B cell interactions in responses of people living with MS, with potential of becoming a biomarker and prognosis tool. Additionally, modulating the dysfunctional targets in Tfr cells, will allow me to understand the impact of the pathways in disease onset and progression, which can contribute to improved therapeutic targets and strategies.Developing this project as a MSCA Postdoctoral Fellow will greatly enhance my scientific and intrapersonal skills, expand my professional network and strongly contribute to my independence as a researcher.