Cutting edge: impaired MHC class I expression in mice deficient for Nlrc5/class I transactivator.

Cutting edge: impaired MHC class I expression in mice deficient for Nlrc5/class I transactivator.
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DOI:
10.4049/jimmunol.1200064
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发表时间:
2012-07-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Kobayashi KS
Kobayashi KS
中科院分区:
其他
文献类型:
--
作者:
Biswas A;Meissner TB;Kawai T;Kobayashi KS

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MHC I类和II类对于适应性免疫系统至关重要。虽然CIITA(Class II transactivator)对MHC II类分子表达的调控早已被认识,但直到最近发现NLRC 5/CITA,MHC I类分子的反式激活机制才被认识。在这里,我们使用NLRC 5缺陷小鼠,NLRC 5是必要的组成型和诱导型MHC I类表达。Nlrc 5的缺失导致MHC I类和相关基因如β 2 m、Tap 1或Lmp 2的表达严重降低,但不影响MHC II类水平。IFN-γ刺激不能克服Nlrc 5缺陷细胞中受损的MHC I类表达。在感染单核细胞增生李斯特菌后,Nlrc 5缺陷小鼠表现出受损的CD 8 + T细胞活化,伴随着细菌负荷增加。这些说明了NLRC 5/CITA在MHC I类基因调控和通过CD 8 + T细胞应答的宿主防御中的关键作用。
MHC class I and class II are crucial for the adaptive immune system. Although regulation of MHC class II expression by CIITA (class II transactivator) has long been recognized, the mechanism of MHC class I transactivation has been largely unknown until the recent discovery of NLRC5/CITA. Here we show using Nlrc5-deficient mice that NLRC5 is required for both constitutive and inducible MHC class I expression. Loss of Nlrc5 resulted in severe reduction in the expression of MHC class I and related genes such as β2m, Tap1 or Lmp2 but did not affect MHC class II levels. IFN-γ stimulation could not overcome the impaired MHC class I expression in Nlrc5-deficient cells. Upon infection with Listeria monocyogenes, Nlrc5-deficient mice displayed impaired CD8+ T cell activation, accompanied with increased bacterial loads. These illustrate critical roles of NLRC5/CITA in MHC class I gene regulation and host defense by CD8+ T cell responses.
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