Caspase-8 Inactivation in T Cells Increases Necroptosis and Suppresses Autoimmunity in \(Bim^{−/−}\) Mice
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Bohgaki, Toshiyuki
Mozo, Julien
Matysiak-Zablocki, Elzbieta
Bohgaki, Miyuki
Sanchez, Otto
Strasser, Andreas
Hakem, Anne
Hakem, Razqallah
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1083/jcb.201103053Metadata
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Bohgaki, Toshiyuki, Julien Mozo, Leonardo Salmena, Elzbieta Matysiak-Zablocki, Miyuki Bohgaki, Otto Sanchez, Andreas Strasser, Anne Hakem, and Razqallah Hakem. 2011. Caspase-8 inactivation in T cells increases necroptosis and suppresses autoimmunity in \(Bim^{−/−}\) mice. The Journal of Cell Biology 195(2): 277-291.Abstract
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 displayed elevated levels of necroptosis and that inhibition of this cell death process fully rescued the survival and proliferation of these cells. Collectively, our data demonstrate that inactivation of caspase-8 suppresses the survival and proliferative capacity of \(Bim^{−/−}\) T cells and restrains autoimmunity in \(Bim^{−/−}\) mice.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198166/pdf/Terms of Use
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