Resident immunity in the multiple sclerosis brain

Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by axon-demyelinating lesions and progressing neuronal decline. Progression and compartmentalized central nervous system (CNS) inflammation are not effectively targeted by current disease-modifying treatments. Therefore, the aim of this thesis is to distinguish mediators and understand pathogenic mechanisms of progressive MS. By thoroughly characterizing the phenotype and acquisition of T cells in non-inflammatory conditions and MS, the importance of CNS immune regulation and compartmentalization is demonstrated. This is consolidated by our findings that the presence and interactions of T cells, B cells, and myeloid cells are differentially regulated in MS. Further, a genetic and pathological basis of MS severity in which an increased CNS-intrinsic propensity to acquire neuro-axonal damage relates to MS severity is disclosed. Together, this reveals MS-associated mechanisms that can be the basis of further research and highlights opportunities for treatments in advanced MS.