Differential requirement for Rel/nuclear factor kappa B family members in natural killer T cell development.

Differential requirement for Rel/nuclear factor kappa B family members in natural killer T cell development.
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DOI:
10.1084/jem.20022234
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发表时间:
2003-06-16
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Weih F
Weih F
中科院分区:
其他
文献类型:
--
作者:
Sivakumar V;Hammond KJ;Howells N;Pfeffer K;Weih F

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自然杀伤T(NKT)细胞参与了从自身免疫抑制到肿瘤排斥的多种免疫应答。胸腺依赖性NKT细胞被主要组织相容性复合物I类分子CD 1d阳性选择,但CD 1d下游的分子事件仍然知之甚少。在这里,我们表明,不同成员的Rel/核因子(NF)-κB家族的转录因子所需的造血和非造血细胞的正常发育的胸腺NKT细胞。表达TCR Vα14-Jα18链的NK-1.1阴性前体细胞转化为成熟NK-1.1阳性NKT细胞需要通过经典IκBα调节途径以细胞自主方式激活NF-κB。另一方面,Rel/NF-κB家族成员RelB必须在辐射抗性胸腺基质细胞中表达,以产生早期NK-1.1阴性NKT前体。此外,NF-κ B诱导激酶(NIK)是RelB与胸腺DNA组成性结合和体外特异性诱导RelB复合物所必需的。因此,造血细胞和非造血细胞中不同的Rel/NF-κB家族成员调节NKT细胞发育,对胸腺基质中NIK介导的Rel B活化具有独特的要求。
Natural killer T (NKT) cells have been implicated in diverse immune responses ranging from suppression of autoimmunity to tumor rejection. Thymus-dependent NKT cells are positively selected by the major histocompatibility complex class I–like molecule CD1d, but the molecular events downstream of CD1d are still poorly understood. Here, we show that distinct members of the Rel/nuclear factor (NF)-κB family of transcription factors were required in both hematopoietic and nonhematopoietic cells for normal development of thymic NKT cells. Activation of NF-κB via the classical IκBα-regulated pathway was required in a cell autonomous manner for the transition of NK-1.1–negative precursors that express the TCR Vα14-Jα18 chain to mature NK-1.1–positive NKT cells. The Rel/NF-κB family member RelB, on the other hand, had to be expressed in radiation resistant thymic stromal cells for the generation of early NK-1.1–negative NKT precursors. Moreover, NF-κB–inducing kinase (NIK) was required for both constitutive thymic DNA binding of RelB and the specific induction of RelB complexes in vitro. Thus, distinct Rel/NF-κB family members in hematopoietic and nonhematopoietic cells regulate NKT cell development with a unique requirement for NIK-mediated activation of RelB in thymic stroma.
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