NIK-dependent RelB activation defines a unique signaling pathway for the development of V alpha 14i NKT cells.
NIK-dependent RelB activation defines a unique signaling pathway for the development of V alpha 14i NKT cells.
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NIK依赖性RELB激活定义了V alpha 14i NKT细胞开发的独特信号通路。
DOI：
10.1084/jem.20030141
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发表时间：
2003-06-16
期刊：
影响因子：
--
通讯作者：
Kronenberg M
中科院分区：
文献类型：
--
作者：
Elewaut D;Shaikh RB;Hammond KJ;De Winter H;Leishman AJ;Sidobre S;Turovskaya O;Prigozy TI;Ma L;Banks TA;Lo D;Ware CF;Cheroutre H;Kronenberg M
Rel B是转录因子的Rel/核因子（NF）-κB家族的成员，其缺陷影响抗原呈递细胞和淋巴器官的形成，但其在T淋巴细胞分化中的作用尚未得到充分表征。在这里，我们表明，小鼠中的RelB缺陷导致NKT细胞的选择性减少。RelB必须在可以是CD 1d阴性的抗辐射宿主细胞中表达，这表明RelB表达细胞不直接有助于CD 1d依赖性NKT细胞的阳性选择。与RelB缺陷小鼠一样，NF-κ B诱导激酶（NIK）突变的aly/aly小鼠NKT细胞数量减少。对aly/aly小鼠胸腺中NKT细胞上NK1.1和CD 44表达的分析揭示了发育的晚期阻滞。在体外，我们表明，NIK是必要的RelB激活后触发的表面受体。通过分析RelB+/− × aly/+复合杂合子小鼠，在体内进一步证明了NIK和RelB之间的这种联系。在用α-GalCer（一种被NKT细胞识别的抗原）刺激后，与RelB+/−或aly/+小鼠相比，这些复合杂合子的反应降低。这些数据说明了NKT细胞发育中造血细胞和非造血细胞类型之间复杂的相互作用，并且它们证明了NKT细胞对由胸腺基质细胞中RelB的NIK激活介导的信号通路的独特需求。
A defect in RelB, a member of the Rel/nuclear factor (NF)-κB family of transcription factors, affects antigen presenting cells and the formation of lymphoid organs, but its role in T lymphocyte differentiation is not well characterized. Here, we show that RelB deficiency in mice leads to a selective decrease of NKT cells. RelB must be expressed in an irradiation-resistant host cell that can be CD1d negative, indicating that the RelB expressing cell does not contribute directly to the positive selection of CD1d-dependent NKT cells. Like RelB-deficient mice, aly/aly mice with a mutation for the NF-κB–inducing kinase (NIK), have reduced NKT cell numbers. An analysis of NK1.1 and CD44 expression on NKT cells in the thymus of aly/aly mice reveals a late block in development. In vitro, we show that NIK is necessary for RelB activation upon triggering of surface receptors. This link between NIK and RelB was further demonstrated in vivo by analyzing RelB+/− × aly/+ compound heterozygous mice. After stimulation with α-GalCer, an antigen recognized by NKT cells, these compound heterozygotes had reduced responses compared with either RelB+/− or aly/+ mice. These data illustrate the complex interplay between hemopoietic and nonhemopoietic cell types for the development of NKT cells, and they demonstrate the unique requirement of NKT cells for a signaling pathway mediated by NIK activation of RelB in a thymic stromal cell.
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影响因子：
32.4
作者：
Dejardin, E;Droin, NM;Green, DR
通讯作者：
Green, DR
影响因子：
--
作者：
FENG, L;XIA, YY;WILSON, CB
通讯作者：
WILSON, CB
影响因子：
15.3
作者：
Benlagha, K;Weiss, A;Beavis, A;Teyton, L;Bendelac, A
通讯作者：
Bendelac, A
影响因子：
64.8
作者：
BEG, AA;SHA, WC;BALTIMORE, D
通讯作者：
BALTIMORE, D
影响因子：
15.3
作者：
Caamano, J H;Rizzo, C A;Durham, S K;Barton, D S;Raventos-Suarez, C;Snapper, C M;Bravo, R
通讯作者：
Bravo, R