The direct deleterious effect of Th17 cells in the nervous system compartment in multiple sclerosis and experimental autoimmune encephalomyelitis: one possible link between neuroinflammation and neurodegeneration

Abstract

Abstract The processes of demyelination and neurodegeneration in the central nervous system (CNS) of multiple sclerosis (MS) patients and experimental autoimmune encephalomyelitis (EAE) are secondary to numerous pathophysiological mechanisms. One of the main cellular players is the Th17 lymphocyte. One of the major functions described for Th17 cells is the upregulation of pro-inflammatory cytokines, such as IL-17 at the level of peripheral and CNS inflammation. This review will focus on the newly described and unexpected, direct role played by the Th17 cells in the CNS of MS patients and EAE models. Th17 and their main cytokine, IL-17, are actively involved in the onset and maintenance of the immune cascade in the CNS compartment as Th17 were found to achieve brain-homing potential. Direct interaction of myelin oligodendrocyte glycoprotein - specific Th17 with the neuronal cells firstly induces demyelination and secondly, extensive axonal damage. The Th17 cells promote an inflammatory B cell response beyond the BBB through the presence of infiltrating Th follicles. Due to their role in preventing remyelination and direct neurotoxic effect, Th17 cells might stand for an important connection between neuroinflammation and neurodegeneration in a devastating disease like MS. The Th17 cell populations have different mechanisms of provoking an autoimmune attack not only in the periphery but also in the CNS of MS patients.