Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8(+) T cells.

Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8(+) T cells.
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DOI:
10.1038/ncomms8089
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发表时间:
2015-05-08
影响因子:
16.6
通讯作者:
Goriely, Stanislas
Goriely, Stanislas
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Martinet, Valerie;Tonon, Sandrine;Torres, David;Azouz, Abdulkader;Muriel Nguyen;Kohler, Arnaud;Flamand, Veronique;Mao, Chai-An;Klein, William H.;Leo, Oberdan;Goriely, Stanislas

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CD8+ T 细胞记忆表型和功能是在抗原驱动激活后获得的。记忆样细胞也可能在胸腺或外周没有抗原暴露的情况下出现。 Eomesodermin (Eomes) 是这些非常规记忆细胞发育的关键转录因子。在此,我们证明 CD8+ T 细胞中的 I 型干扰素信号传导直接激活 Eomes 基因表达。与这一观察结果一致,“虚拟记忆”CD8+ T 细胞的表型、功能和年龄依赖性扩张在 I 型干扰素信号传导缺失的情况下受到强烈影响。此外,I 型干扰素以 Eomes 依赖性方式诱导“虚拟记忆”CD8+ T 细胞持续扩增。我们进一步表明,“先天胸腺”CD8+ T 细胞的发育依赖于相同的途径。总之,我们证明 CD8+ T 细胞中的 I 型干扰素信号传导驱动 Eomes 表达,从而调节记忆样 CD8+ T 细胞的功能和稳态。 脱中胚蛋白是“虚拟记忆”T 细胞发育的关键转录因子,这种细胞在没有抗原驱动激活的情况下发育。作者在此表明,I 型干扰素直接激活中胚层蛋白并有助于虚拟记忆 CD8+ T 细胞的稳态。
CD8+ T-cell memory phenotype and function are acquired after antigen-driven activation. Memory-like cells may also arise in absence of antigenic exposure in the thymus or in the periphery. Eomesodermin (Eomes) is a key transcription factor for the development of these unconventional memory cells. Herein, we show that type I interferon signalling in CD8+ T cells directly activates Eomes gene expression. Consistent with this observation, the phenotype, function and age-dependent expansion of ‘virtual memory' CD8+ T cells are strongly affected in absence of type I interferon signalling. In addition, type I interferons induce a sustained expansion of ‘virtual memory' CD8+ T cells in an Eomes-dependent fashion. We further show that the development of ‘innate thymic' CD8+ T cells is dependent on the same pathway. In conclusion, we demonstrate that type I interferon signalling in CD8+ T cells drives Eomes expression and thereby regulates the function and homeostasis of memory-like CD8+ T cells. Eomesodermin is the key transcription factor for the development of ‘virtual memory' T cells that develop in the absence of antigen-driven activation. Here the authors show that type I interferons directly activate eomesodermin and contribute to the homeostasis of virtual memory CD8+ T cells.
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