Published in:
Open Access
01-12-2012 | Oral presentation
Death receptor-induced apoptosis signalling - essential guardian against autoimmune disease
Authors:
Andreas Strasser, Lorraine A O'Reilly, Philipp Jost, Thomas Kaufmann, Stephanie Grabow, Elizabeth Kruse, Lin Tai, Mark Smyth, Philippe Bouillet
Published in:
Arthritis Research & Therapy
|
Special Issue 1/2012
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Excerpt
The FasL/Fas system is critical for deletion of autoreactive and antigen-activated T and B cells. Accordingly, mutations in these proteins result in lymphadenopathy and autoimmunity in gld and lpr mutant mice, which lack functional FasL or Fas, respectively. Upon antigenic stimulation of T cells, FasL is sythesised, directed to and stored in secretory lysosomes followed by extrusion at the immunological synapse where it is rapidly downregulated by a metalloprotease, shedding the extracellular portion (sFasL) to prevent non-specific killing. It is unclear whether the pathology observed in gld mutant mice is due to the loss of the membrane-bound or the secreted form of FasL or both. …
