Autoimmune function of ectopic lymphoid follicles in multiple sclerosis (MS)

• Applicant: Sarah McGrath, Ph.D.
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Immunology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 568898367

Multiple sclerosis (MS) is the most common autoimmune neurological disease, affecting 2.5 million people worldwide and is particularly prevalent in Western Europe, where MS contributed to 262,909 disability-adjusted life years (1990-2016). The most significant unmet clinical need is in the progressive stages of MS, which currently lack effective treatments. Understanding MS pathogenesis, especially in these stages, is vital for developing therapies that enhance quality of life and reduce disability. Ectopic lymphoid follicles (eLFs) are clusters of B and T cells, observed in 40-60% of people with (pw)MS and associated with progressive disease and severe pathology. The mechanisms of eLF formation and their functional roles, particularly in driving local autoimmunity, remain poorly understood. The host, Dr. Peters, has developed a novel in vivo EAE model that uniquely forms eLF structures in the CNS meninges. Applying this model with advanced technologies at the host institute, I will uncover mechanisms of eLF formation driven by Th17 cells and subsequent development of B cell specificities within MS-associated eLFs. In addition, leveraging my translational immunology background and in collaboration with the spatial omics facility at TUM, I will also determine the immunophenotype and clonal response of eLFs in human MS eLFs. This project will generate critical new insights to the cellular and molecular mechanisms underlying eLF formation in MS, addressing a significant gap in our understanding of progressive disease. By integrating advanced experimental models with spatially resolved analysis of human tissue, the work has the potential to inform the development of future therapies targeting CNS-compartmentalised autoimmunity. Concurrently, the project is designed to support my scientific development in neuroimmunology and eLF biology, and by equipping me with the methodological and analytical skills required to pursue an independent research career in the field of autoimmune eLFs.

• DFG Programme: WBP Position