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Fas-Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis
Elisabetta Volpe1, Manolo Sambucci1, Luca Battistini1
1Neuroimmunology Unit, Santa Lucia Foundation , Rome , Italy.
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.
Insights
The Fas-FasL pathway regulates T cell death, crucial for preventing autoimmunity like multiple sclerosis (MS). This review explores its role in MS, including its impact on T helper 17 and T regulatory cells.
Area of Science:
- Immunology
- Cell Biology
- Neuroimmunology
Background:
- The Fas and Fas Ligand (FasL) pathway is critical for regulating apoptosis, including negative selection of T cells and activation-induced cell death.
- Dysregulation of the Fas-FasL pathway is implicated in the pathogenesis of autoimmune diseases, exemplified by multiple sclerosis (MS).
- Recent research highlights the roles of T helper 17 (Th17) and T regulatory (Treg) cells in MS pathogenesis and immune regulation.
Approach:
- This review synthesizes current knowledge on the Fas-FasL pathway's function in the context of multiple sclerosis.
- It examines the mechanisms by which Fas-FasL signaling influences T cell homeostasis and immune responses relevant to MS.
- The review specifically investigates the interplay between Fas-FasL and the distinct functions of Th17 and Treg cells in MS.
Key Points:
- Fas-FasL-mediated apoptosis is essential for maintaining T cell tolerance and preventing autoimmune responses.
- Defects in Fas or FasL function are linked to the development of autoimmune diseases, including MS.
- The Fas-FasL pathway modulates the balance between pathogenic Th17 cells and protective Treg cells in MS.
Conclusions:
- The Fas-FasL pathway plays a significant role in the immune dysregulation observed in multiple sclerosis.
- Understanding Fas-FasL interactions with Th17 and Treg cells offers potential therapeutic targets for MS.
- Further research into this pathway could elucidate novel strategies for managing MS and other autoimmune conditions.
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