Fas ligand

A protein involved in the regulation of the immune system

Overview

Fas ligand (FasL) is a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. It plays a crucial role in the regulation of the immune system and the induction of apoptosis, or programmed cell death. FasL is primarily expressed on the surface of activated T cells and natural killer cells, and it interacts with its receptor, Fas receptor (FasR), to trigger apoptotic signaling pathways.

Structure

Fas ligand is a homotrimeric protein, meaning it forms a complex of three identical subunits. Each subunit consists of an extracellular domain, a transmembrane domain, and a short cytoplasmic tail. The extracellular domain is responsible for binding to the Fas receptor, initiating the apoptotic cascade.

Function

The primary function of Fas ligand is to induce apoptosis in target cells. This is a critical mechanism for maintaining immune homeostasis and preventing autoimmune diseases. When FasL binds to FasR on the surface of a target cell, it triggers a series of intracellular events that lead to cell death. This process is essential for the elimination of infected or cancerous cells and for the termination of immune responses.

Role in Immune System

Fas ligand is involved in several key processes within the immune system:

• Activation-Induced Cell Death (AICD): FasL is crucial for AICD, a process that helps regulate the immune response by eliminating excess lymphocytes after an immune response.
• Peripheral Tolerance: FasL contributes to peripheral tolerance by inducing apoptosis in self-reactive T cells, thus preventing autoimmunity.
• Cytotoxic T Lymphocyte (CTL) Function: CTLs use FasL to kill target cells, such as virus-infected cells or tumor cells, by inducing apoptosis.

Pathology

Dysregulation of Fas ligand or its receptor can lead to various diseases:

• Autoimmune Diseases: Insufficient FasL activity can result in the survival of self-reactive lymphocytes, contributing to autoimmune conditions such as systemic lupus erythematosus and rheumatoid arthritis.
• Cancer: Some cancer cells evade immune surveillance by downregulating FasR or expressing FasL to induce apoptosis in attacking immune cells.
• Immunodeficiency: Mutations in the Fas or FasL genes can lead to immunodeficiency syndromes, characterized by lymphoproliferation and increased susceptibility to infections.

Clinical Applications

Understanding the Fas/FasL system has implications for therapeutic interventions:

• Cancer Therapy: Strategies to enhance FasL-mediated apoptosis in tumor cells are being explored as potential cancer treatments.
• Autoimmune Disease Treatment: Modulating FasL activity could help in treating autoimmune diseases by promoting the deletion of autoreactive lymphocytes.

Images

File:FasL structure.png

Diagram of Fas ligand structure showing its trimeric form.

File:FasL pathway.png

Illustration of the Fas/FasL apoptotic pathway.

Related pages

• Apoptosis
• Tumor necrosis factor
• Immune system
• T cell
• Natural killer cell