AUTHOR=Volpe Elisabetta , Sambucci Manolo , Battistini Luca , Borsellino Giovanna 

TITLE=Fas–Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 7 - 2016

YEAR=2016

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00382

DOI=10.3389/fimmu.2016.00382

ISSN=1664-3224

ABSTRACT=Fas and Fas Ligand (FasL) are two molecules involved in regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor genes (TCR) 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, then we discuss recent advances concerning the role of Fas-FasL in regulating Th17 and Treg cells’ functions, in the context of MS.