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Nature Medicine:Notch信号通路控制CD4阳性记忆T细胞的存活

来源:生物谷 2015-01-16 10:54

2015年1月16日讯 /生物谷BIOON/ --为了保护机体免于遭受将来相同的病原体感染,CD4阳性T细胞能分化成记忆T细胞。于此相对的,还有一群名为自主活化的CD4阳性记忆T细胞会持续存在于组织中造成对身体的破坏。然而机体如何控制CD4阳性记忆T细胞种群稳定的详细机制还不清楚。

本文的研究者们发现Notch信号通路中的一个蛋白Rbpj(recombination signal biding protein for immunoglobulin k J region)受损后CD4阳性记忆T细胞的生存能力也受到遏制。对小鼠使用Notch信号通路的抑制剂也能减少CD4阳性记忆T细胞的种群数量,并能够预防实验性自身免疫型脑脊髓炎的复发。Pbpj缺陷的CD4阳性记忆T细胞表现出葡萄糖摄取减少,而背后的分子机制是由于Akt磷酸化的降低导致葡萄糖转运蛋白Glut1低表达造成的。

而通过给予Pbpj敲除小鼠丙酮酸(能够绕过葡萄糖摄取而作为底物直接供给三羧酸循环),可以抑制自助活化的CD4阳性记忆T细胞,说明CD4阳性记忆T细胞的存活依赖于葡萄糖代谢。

总的来说,文章阐释了Notch信号通路通过调节葡萄糖摄取来维持CD4阳性记忆T细胞的功能。(生物谷Bioon.com)

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Nature Medicine doi:10.1038/nm.3758

Notch controls the survival of memory CD4+ T cells by regulating glucose uptake

Yoichi Maekawa, Chieko Ishifune, Shin-ichi Tsukumo, Katsuto Hozumi, Hideo Yagita & Koji Yasutomo

CD4+ T cells differentiate into memory T cells that protect the host from subsequent infection. In contrast, autoreactive memory CD4+ T cells harm the body by persisting in the tissues. The underlying pathways controlling the maintenance of memory CD4+ T cells remain undefined. We show here that memory CD4+ T cell survival is impaired in the absence of the Notch signaling protein known as recombination signal binding protein for immunoglobulin κ J region (Rbpj). Treatment of mice with a Notch inhibitor reduced memory CD4+ T cell numbers and prevented the recurrent induction of experimental autoimmune encephalomyelitis. Rbpj-deficient CD4+ memory T cells exhibit reduced glucose uptake due to impaired AKT phosphorylation, resulting in low Glut1 expression. Treating mice with pyruvic acid, which bypasses glucose uptake and supplies the metabolite downstream of glucose uptake, inhibited the decrease of autoimmune memory CD4+ T cells in the absence of Notch signaling, suggesting memory CD4+ T cell survival relies on glucose metabolism. Together, these data define a central role for Notch signaling in maintaining memory CD4+ T cells through the regulation of glucose uptake.

 


 

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