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Caspase-8 inactivation in T cells increases necroptosis and suppresses autoimmunity in Bim(-/-) mice


Bohgaki, T; Mozo, J; Salmena, L; Matysiak-Zablocki, E; Bohgaki, M; Sanchez, O; Strasser, A; Hakem, A; Hakem, R
2011-10-17
JOURNAL OF CELL BIOLOGY
Journal Article
195
2
277-291
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.
ROCKEFELLER UNIV PRESS
NF-KAPPA-B; FAMILY-MEMBER BIM; SYSTEMIC AUTOIMMUNITY; AUTOREACTIVE THYMOCYTES; MOLECULAR-MECHANISMS; IMMUNE-RESPONSES; REGULATORS BIM; DEATH PATHWAY; FAS; HOMEOSTASIS
10.1083/jcb.201103053
Refer to copyright notice on published article.

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Creation Date 2011-10-17 12:00:00