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Apoptosis mediated by the Fas system

S Nagata1

  • 1Osaka Bioscience Institute, Japan.

Progress in Molecular and Subcellular Biology
|January 1, 1996
PubMed

Insights

The Fas system, involving Fas and Fas ligand, regulates T-cell apoptosis crucial for immune homeostasis. Mutations in Fas or Fas ligand cause autoimmune diseases and lymphoproliferation in mice.

Area of Science:

  • Immunology
  • Cell Biology
  • Genetics

Background:

  • Fas is a cell-surface protein that mediates apoptosis.
  • Fas ligand, a type II membrane protein, induces apoptosis by binding to Fas and is expressed on activated T cells.
  • The Fas system plays a critical role in lymphocyte development and immune regulation.

Purpose of the Study:

  • To investigate the role of the Fas system in T-cell development and apoptosis.
  • To understand the implications of Fas and Fas ligand mutations in autoimmune diseases.
  • To explore the involvement of the Fas system in cytotoxic T-lymphocyte-mediated pathology.

Main Methods:

  • Molecular and genetic analysis of Fas and Fas ligand.
  • Phenotypic analysis of mouse models with lymphoproliferation (lpr) and generalized lymphoproliferative disease (gld) mutations.
  • Administration of agonistic anti-Fas antibody in mice.

Main Results:

  • Mouse mutations lpr and gld correspond to defects in Fas and Fas ligand, respectively.
  • Mice with lpr or gld mutations exhibit lymphadenopathy and autoimmune disease.
  • Fas is expressed in non-lymphoid organs like the liver, heart, and lung.
  • Anti-Fas antibody administration induces lethal liver apoptosis in mice.

Conclusions:

  • The Fas system is essential for peripheral T-cell deletion and activation-induced cell death.
  • Fas and Fas ligand mutations lead to autoimmune disorders.
  • The Fas system is implicated in physiological processes and pathological conditions like fulminant hepatitis.

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