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The Role of Fas Ligand in Beta Cell Destruction in Autoimmune Diabetes of NOD Mice
Author(s) -
PETROVSKY N.,
SILVA D.,
SOCHA L.,
SLATTERY R.,
CHARLTON B.
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb02970.x
Subject(s) - fas ligand , apoptosis , immune privilege , biology , nod mice , programmed cell death , microbiology and biotechnology , cytokine , beta (programming language) , beta cell , immunology , cancer research , immune system , autoimmunity , endocrinology , diabetes mellitus , islet , biochemistry , computer science , programming language
A bstract : 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.