Fas ligand (FasL), a type 2 membrane protein belonging to the TNF family, plays an important role in the induction of cell death. Ligation of Fas receptors by FasL results in apoptosis of the Fas-expressing cell. Autoimmune diabetes results from β cell destruction by islet-reactive T cells, a process that involves β cell apoptosis. This raises the question of whether the FasL-Fas pathway plays a major role in β cell death. To address this issue it is important to know whether β cells express Fas and/or FasL and, if so, whether induction of these molecules leads to β cell death. In fact, both Fas and FasL have been demonstrated to be expressed by β cells in response to cytokine stimulation, although there remains an argument in the literature as to whether β cells truly express FasL. This is largely because FasL expression has only been demonstrable by immunohistochemistry and not by flow cytometry. Transgenic NOD mice with β cells expressing a FasL transgene develop an accelerated form of diabetes. We show here that β cells from FasL transgenic NOD mice are more susceptible to cytokine-induced apoptosis than wild-type β cells, consistent with the hypothesis that if β cells express FasL then Fas-FasL interaction on the β cell surface is able to mediate β cell self-death in the absence of T cells. Interventions that block the Fas-FasL pathway may be useful, therefore, in the prevention or treatment of type 1 diabetes.
|Number of pages||5|
|Journal||Annals of the New York Academy of Sciences|
|Publication status||Published - Apr 2002|
- Fas ligand
- NOD mice