Immunologic Aspects of Multiple Sclerosis

Abstract

Multiple sclerosis is an inflammatory and degenerative disease of the central nervous system characterized by demyelination and axonal loss. Genetic and environmental factors contribute to the risk of immune dysregulation in multiple sclerosis. The review focuses on the immunopathogenic role played by various lymphocyte subsets and their cytokine products in the onset and disease progression, and the role of regulatory immune cells in disease remission. The mechanism of action of approved and experimental therapies, and how these mechanisms support the immunopathogenesis paradigm, is also reviewed.

Elucidating the Molecular Basis of Multiple Sclerosis and Understanding the Disease Pathophysiology

“…Moreover, immature and regulatory DC can induce peripheral tolerance and regulate T-cell development [3].…”

“…IL-1β and IL-23, on the other hand, stimulate Th17 cell differentiation. Finally, FOXP3+ Treg cell differentiation is promoted by TGF-β [3].…”

“…Both helper CD4+ T-cells and cytotoxic CD8+ T-cells have been correlated with MS plaques. Moreover, several subpopulations of CD4+ T-cells, including Th17, Th1 and Th2 cells, were associated with MS lesions in the past [3]. In fact, some seem to think that CD4+ T-cells suffice to develop the disease, as transgenic mice that express both HLA-DRB*15:01 and human TCR that recognize myelin-basic protein (MBP) spontaneously develop MS-like disease.…”

“…The latter two also bind CCL20 expressed on Th17 cells in response to TGF-β and IL-6 and in the presence of STAT3, RORγ and IL-21. Thus, polymorphisms noted in TGFB1, the T+869C (Leu10Pro), and in STAT3, rs9891119, could induce MS not only by inducing Th17 differentiation but also by inducing their migration [2,3,15,62,64,65].…”

“…Several pieces of evidence have supported the role of Th17 cells in the initiation and relapse stages of MS. Th17 cell suppression could in part be mediated by peroxisome proliferator-activated receptor gamma (PPAR-γ) molecules that inhibit TGF-β/IL-6-induced expression of RORγt [3]. In fact, increased expression of PPAR-γ in MS patients has already been reported [66].…”