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Caspase-8 inactivation in T cells increases necroptosis and suppresses autoimmunity in Bimmice.

J Cell Biol.. 2011-10;  195(2):277 - 291
Toshiyuki Bohgaki, Toshiyuki Bohgaki, Julien Mozo, Julien Mozo, Leonardo Salmena, Leonardo Salmena, Elzbieta Matysiak-Zablocki, Elzbieta Matysiak-Zablocki, Miyuki Bohgaki, Miyuki Bohgaki, Otto Sanchez, Otto Sanchez, Andreas Strasser, Anne Hakem, Andreas Strasser, Razqallah Hakem, Anne Hakem, and Razqallah Hakem. Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
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摘要

Dysregulation of either the extrinsic or intrinsic apoptotic pathway can lead to various diseases including immune disorders and cancer. In addition to its role in the extrinsic apoptotic pathway, caspase-8 plays nonapoptotic functions and is essential for T cell homeostasis. The pro-apoptotic BH3-only Bcl-2 family member Bim is important for the intrinsic apoptotic pathway and its inactivation leads to autoimmunity that is further exacerbated by loss of function of the death receptor Fas. We report that inactivation of caspase-8 in T cells of Bim(-/-) mice restrained their autoimmunity and extended their life span. We show that, similar to caspase-8(-/-) T cells, Bim(-/-) T cells that also lack caspase-8 displ... More

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