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

被引：24

作者：

Bohgaki, Toshiyuki ^{[1
,2
]}

Mozo, Julien ^{[1
,2
]}

Salmena, Leonardo ^{[3
]}

Matysiak-Zablocki, Elzbieta ^{[1
,2
]}

Bohgaki, Miyuki ^{[1
,2
]}

Sanchez, Otto ^{[4
]}

Strasser, Andreas ^{[5
]}

Hakem, Anne ^{[1
,2
]}

Hakem, Razqallah ^{[1
,2
]}

机构：

[1] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada

[2] Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada

[3] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Canc Genet Program, Boston, MA 02215 USA

[4] Univ Ontario Inst Technol, Oshawa, ON L1H 7K4, Canada

[5] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia

来源：

JOURNAL OF CELL BIOLOGY | 2011年 / 195卷 / 02期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

NF-KAPPA-B; FAMILY-MEMBER BIM; SYSTEMIC AUTOIMMUNITY; AUTOREACTIVE THYMOCYTES; MOLECULAR-MECHANISMS; IMMUNE-RESPONSES; REGULATORS BIM; DEATH PATHWAY; FAS; HOMEOSTASIS;

D O I：

10.1083/jcb.201103053

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

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 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.

引用

页码：277 / 291

页数：15

共 59 条

[1]

FADD and caspase-8 control the outcome of autophagic signaling in proliferating T cells [J].