Caspase-8 inactivation in T cells increases necroptosis and suppresses autoimmunity in Bim-/- mice.
Caspase-8 inactivation in T cells increases necroptosis and suppresses autoimmunity in Bim-/- mice.
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DOI：
10.1083/jcb.201103053
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发表时间：
2011-10-17
期刊：
影响因子：
--
通讯作者：
Hakem R
中科院分区：
文献类型：
--
作者：
Bohgaki T;Mozo J;Salmena L;Matysiak-Zablocki E;Bohgaki M;Sanchez O;Strasser A;Hakem A;Hakem R
在缺乏促凋亡因子Bim的情况下，caspase-8通过诱导T细胞死亡来抑制自身免疫发挥重要作用。外在或内在凋亡通路的失调可导致多种疾病，包括免疫紊乱和癌症。除了在外源性凋亡通路中发挥作用外，caspase-8还具有非凋亡功能，对T细胞稳态至关重要。促凋亡的BH3-only Bcl-2家族成员Bim对内在凋亡途径很重要，其失活导致自身免疫，死亡受体Fas功能丧失进一步加剧自身免疫。我们报道了Bim - / -小鼠T细胞中caspase-8的失活抑制了它们的自身免疫并延长了它们的寿命。我们发现，与caspase-8 - / - T细胞类似，缺乏caspase-8的Bim - / - T细胞也表现出坏死坏死水平升高，抑制这种细胞死亡过程完全挽救了这些细胞的存活和增殖。总的来说，我们的数据表明caspase-8的失活抑制了Bim - / - T细胞的存活和增殖能力，并抑制了Bim - / -小鼠的自身免疫。
In the absence of the pro-apoptotic factor Bim, caspase-8 plays an important role in restraining autoimmunity by inducing cell death in T cells. 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.
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影响因子：
32.4
作者：
Hughes, Peter D.;Belz, Gabrielle T.;Fortner, Karen A.;Budd, Ralph C.;Strasser, Andreas;Bouillet, Philippe
通讯作者：
Bouillet, Philippe
影响因子：
15.3
作者：
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通讯作者：
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作者：
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14.8
作者：
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影响因子：
4.8
作者：
Lemmers, Benedicte;Salmena, Leonardo;Hakem, Anne
通讯作者：
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