Chronic activation of the kinase IKKβ impairs T cell function and survival.
Chronic activation of the kinase IKKβ impairs T cell function and survival.
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DOI：
10.4049/jimmunol.1102429
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发表时间：
2012-08-01
期刊：
影响因子：
--
通讯作者：
Zhong XP
中科院分区：
文献类型：
--
作者：
Krishna S;Xie D;Gorentla B;Shin J;Gao J;Zhong XP
Activation of the transcription factor NF-κB is critical for cytokine production and T cell survival after T cell receptor (TCR) engagement. The effects of persistent NF-κB activity on T cell function and survival are poorly understood. In this study, using a murine model that expresses a constitutively active form of inhibitor of κB kinase β(caIKKβ) in a T-cell specific manner, we demonstrate that chronic IKKβ signaling promotes T cell apoptosis, attenuates responsiveness to TCR-mediated stimulation in vitro, and impairs T cell responses to bacterial infection in vivo. CaIKKβ T cells showed increased FasL expression and caspase-8 activation, and blocking Fas/FasL interactions enhanced cell survival. T cell unresponsiveness was associated with defects in TCR proximal signaling, and elevated levels of Blimp1, a transcriptional repressor that promotes T cell exhaustion. CaIKKβ T cells also showed a defect in IL-2 production, and addition of exogenous IL-2 enhanced their survival and proliferation. Conditional deletion of Blimp1 partially rescued sensitivity of caIKKβ T cells to TCR triggering. Furthermore, adoptively transferred caIKKβ T cells showed diminished expansion and increased contraction in response to infection with Listeria monocytogenes expressing a cognate antigen. Despite their functional defects, caIKKβ T cells readily produced pro-inflammatory cytokines and mice developed autoimmunity. In contrast to NF-κB's critical role in T cell activation and survival, our study demonstrates that persistent IKK-NF-κB signaling is sufficient to impair both T cell function and survival.
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影响因子：
4.4
作者：
Mattioli, I;Sebald, A;Schmitz, ML
通讯作者：
Schmitz, ML
DOI：
10.1073/pnas.142298399
发表时间：
2002-07-09
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
15.3
作者：
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通讯作者：
Kopf, M