西亚试剂：低营养水平和衰老信号促进T细胞衰老机制

在以往的研究中，伦敦大学学院的Arne Akbar教授研究小组证实，称作为“T淋巴细胞”的免疫系统细胞衰老受到“p38 MAPK”分子的控制，后者作为刹车阻止了某些细胞功能。他们发现，采用p38 MAPK抑制剂可以逆转这一刹车作用，表明采用药物治疗有可能让衰老的T细胞恢复青春。

在发表于今天《自然免疫学》(Nature Immunology)杂志上的一项新研究中，该研究小组证实低营养水平加上年龄(衰老)相关的一些信号激活了p38 MAPK。

人们很早以前就怀疑，营养物质、代谢和免疫之间有关联，这篇论文提供了营养物质和衰老信号集中调控T淋巴细胞功能的一个典型机制。 这项研究还证实，通过阻断与此过程相关的一个分子可以重建衰老T淋巴细胞的功能。

原文摘要：

The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells

Alessio Lanna, Sian M Henson, David Escors & Arne N Akbar

In T lymphocytes, the mitogen-activated protein kinase (MAPK) p38 regulates pleiotropic functions and is activated by canonical MAPK signaling or the alternative activation pathway downstream of the T cell antigen receptor (TCR). Here we found that senescent human T cells lacked the canonical and alternative pathways for the activation of p38 but spontaneously engaged the metabolic master regulator AMPK to trigger recruitment of p38 to the scaffold protein TAB1, which caused autophosphorylation of p38. Signaling via this pathway inhibited telomerase activity, T cell proliferation and the expression of key components of the TCR signalosome. Our findings identify a previously unrecognized mode for the activation of p38 in T cells driven by intracellular changes such as low-nutrient and DNA-damage signaling (an 'intrasensory' pathway). The proliferative defect of senescent T cells was reversed by blockade of AMPK-TAB1–dependent activation of p38.

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