Related Experiment Videos
Apoptosis in SLE--too little or too much?
1Specialized Center of Research (SCOR) in SLE, Hospital for Special Surgery, Cornell University Medical College, New York, NY 10021.
Abstract:
Cells of the immune system are, most likely, programmed to die unless recruited into an immune response. An active cell death program may also be induced by a variety of soluble and surface signals, many of which have only recently been recognized. The importance of these pathways in maintaining tolerance is highlighted by the development of lupus-like diseases in three different mouse strains that have spontaneous mutations in the Fas/APO-1 receptor or its ligand. The known function of Fas/APO-1 in signalling apoptosis explains the persistence of self reactive cells in lpr mice although it is unclear, at present, whether Fas defects effect both central and peripheral tolerance. Whereas Fas/APO-1 receptor expression appears to be normal in humans with SLE, other defects in the Fas/APO-1 pathway or other key molecules in the cell death survival require further study.
Insights
Immune cells undergo programmed cell death unless activated. Defects in the Fas/APO-1 pathway, crucial for immune tolerance, can lead to lupus-like diseases in mice.
Area of Science:
- Immunology
- Cell Biology
- Autoimmunity
Background:
- Immune system cells are programmed for death unless activated by immune responses.
- Soluble and surface signals can induce active cell death pathways.
- These pathways are critical for maintaining self-tolerance.
Purpose of the Study:
- To investigate the role of Fas/APO-1 pathway in immune tolerance.
- To understand the implications of Fas/APO-1 defects in autoimmune diseases like lupus.
Main Methods:
- Analysis of mouse models with spontaneous mutations in the Fas/APO-1 receptor or its ligand.
- Examination of immune cell persistence in relation to Fas/APO-1 function.
- Comparison of Fas/APO-1 pathway in humans with Systemic Lupus Erythematosus (SLE).
Main Results:
- Mutations in Fas/APO-1 or its ligand cause lupus-like diseases in mice.
- Fas/APO-1 signaling defects explain the persistence of self-reactive cells in lpr mice.
- Fas/APO-1 receptor expression is normal in human SLE, suggesting other pathway defects.
Conclusions:
- The Fas/APO-1 pathway is vital for immune tolerance, and its defects contribute to autoimmunity.
- Further research is needed to identify other molecular defects in the Fas/APO-1 pathway or cell death/survival pathways in SLE.