title: Fas-Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis.
abstract: Fas and Fas Ligand (FasL) are two molecules involved in the regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor (TCR) genes and of those that recognize self-antigens, a process called negative selection; moreover, Fas-FasL interaction leads to activation-induced cell death, a form of apoptosis induced by repeated TCR stimulation, responsible for the peripheral deletion of activated T cells. Both control mechanisms are particularly relevant in the context of autoimmune diseases, such as multiple sclerosis (MS), where T cells exert an immune response against self-antigens. This concept is well demonstrated by the development of autoimmune diseases in mice and humans with defects in Fas or FasL. In recent years, several new aspects of T cell functions in MS have been elucidated, such as the pathogenic role of T helper (Th) 17 cells and the protective role of T regulatory (Treg) cells. Thus, in this review, we summarize the role of the Fas-FasL pathway, with particular focus on its involvement in MS. We then discuss recent advances concerning the role of Fas-FasL in regulating Th17 and Treg cells' functions, in the context of MS.
authors.affiliation: Neuroimmunology Unit, Santa Lucia Foundation , Rome , Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Volpe
authors.affiliation: Neuroimmunology Unit, Santa Lucia Foundation , Rome , Italy.
authors.forename: Manolo
authors.initials: M
authors.lastname: Sambucci
authors.affiliation: Neuroimmunology Unit, Santa Lucia Foundation , Rome , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Battistini
authors.affiliation: Neuroimmunology Unit, Santa Lucia Foundation , Rome , Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Borsellino
keywords: Fas–FasL; T regulatory cells; Thelper 17 cells; cell death; multiple sclerosis