Transmission of survival signals through Delta-like 1 on activated CD4(+) T cells.
Transmission of survival signals through Delta-like 1 on activated CD4(+) T cells.
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DOI：
10.1038/srep33692
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发表时间：
2016-09-23
影响因子：
4.6
通讯作者：
Yasutomo K
中科院分区：
文献类型：
--
作者：
Furukawa T;Ishifune C;Tsukumo SI;Hozumi K;Maekawa Y;Matsui N;Kaji R;Yasutomo K
表达在CD4+T细胞上的Noch传递信号，调节其效应器功能和生存。虽然已知Notch信号被表达在同一细胞上的Notch配体顺式抑制，但Notch配体在T细胞上的作用尚不清楚。在这份报告中，我们证明了CD4+T细胞Notch配体Dll1传递生存所需的信号。将DLL1−/−小鼠和对照小鼠的CD+T细胞共同转移到受体小鼠中，然后进行免疫，结果显示，与对照细胞相比，DL11−/−小鼠的CD+T细胞迅速下降。DLL1−/−小鼠实验性自身免疫性脑炎的临床评分低于对照组。DLL1−/−小鼠CD4+T细胞中Notch靶基因的表达未受影响，提示DLL1缺陷不影响顺式Notch信号转导。在缺乏Dll1的CD4+T细胞中过表达Dll1的胞内区可以部分挽救受损的生存。我们的数据表明，Dll1是Notch信号的独立调节者，对激活的CD4+T细胞的生存至关重要，并为了解Notch配体的生理作用以及维持适应性免疫反应的重要调节机制提供了新的见解。
Notch expressed on CD4+ T cells transduces signals that mediate their effector functions and survival. Although Notch signaling is known to be cis-inhibited by Notch ligands expressed on the same cells, the role of Notch ligands on T cells remains unclear. In this report we demonstrate that the CD4+ T cell Notch ligand Dll1 transduces signals required for their survival. Co-transfer of CD4+ T cells from Dll1−/− and control mice into recipient mice followed by immunization revealed a rapid decline of CD4+ T cells from Dll1−/− mice compared with control cells. Dll1−/− mice exhibited lower clinical scores of experimental autoimmune encephalitis than control mice. The expression of Notch target genes in CD4+ T cells from Dll1−/− mice was not affected, suggesting that Dll1 deficiency in T cells does not affect cis Notch signaling. Overexpression of the intracellular domain of Dll1 in Dll1-deficient CD4+ T cells partially rescued impaired survival. Our data demonstrate that Dll1 is an independent regulator of Notch-signaling important for the survival of activated CD4+ T cells, and provide new insight into the physiological roles of Notch ligands as well as a regulatory mechanism important for maintaining adaptive immune responses.
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影响因子：
11.4
作者：
Glittenberg, Marcus;Pitsouli, Chrysoula;Bray, Sarah
通讯作者：
Bray, Sarah
扩大了CD4⁺T细胞对病毒免疫的作用。
DOI：
10.1038/nri3152
发表时间：
2012-01-20
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.6
作者：
Brooker, R;Hozumi, K;Lewis, J
通讯作者：
Lewis, J
DOI：
10.1073/pnas.1206044109
发表时间：
2012-06-05
影响因子：
11.1
作者：
Helbig, Christina;Gentek, Rebecca;Amsen, Derk
通讯作者：
Amsen, Derk
影响因子：
3.7
作者：
Formosa-Jordan P;Ibañes M
通讯作者：
Ibañes M