Transcription factor networks in aged naïve CD4 T cells bias lineage differentiation.,Aging Cell

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Transcription factor networks in aged naïve CD4 T cells bias lineage differentiation.
Aging Cell ( IF 8.0 ) Pub Date : 2019-07-01 , DOI: 10.1111/acel.12957
Bin Hu _{1,

2} , Guangjin Li ₂ , Zhongde Ye ₂ , Claire E Gustafson _{1,

2} , Lu Tian ₃ , Cornelia M Weyand _{1,

2} , Jörg J Goronzy _{1,

2}

Affiliation

With reduced thymic activity, the population of naïve T cells in humans is maintained by homeostatic proliferation throughout adult life. In young adults, naïve CD4 T cells have enormous proliferative potential and plasticity to differentiate into different lineages. Here, we explored whether naïve CD4 T‐cell aging is associated with a partial loss of this unbiased multipotency. We find that naïve CD4 T cells from older individuals have developed a propensity to develop into TH9 cells. Two major mechanisms contribute to this predisposition. First, responsiveness to transforming growth factor β (TGFβ) stimulation is enhanced with age due to an upregulation of the TGFβR3 receptor that results in increased expression of the transcription factor PU.1. Secondly, aged naïve CD4 T cells display altered transcription factor profiles in response to T‐cell receptor stimulation, including enhanced expression of BATF and IRF4 and reduced expression of ID3 and BCL6. These transcription factors are involved in TH9 differentiation as well as IL9 transcription suggesting that the aging‐associated changes in the transcription factor profile favor TH9 commitment.

中文翻译：

老年幼稚 CD4 T 细胞中的转录因子网络偏向谱系分化。

随着胸腺活性的降低，人类中幼稚 T 细胞的数量在整个成年过程中通过稳态增殖得以维持。在年轻人中，幼稚 CD4 T 细胞具有巨大的增殖潜力和分化成不同谱系的可塑性。在这里，我们探讨了幼稚 CD4 T 细胞的衰老是否与这种无偏多能性的部分丧失有关。我们发现，来自老年人的幼稚 CD4 T 细胞有发育成 TH9 细胞的倾向。有两个主要机制导致了这种倾向。首先，由于 TGFβR3 受体上调，导致转录因子 PU.1 表达增加，对转化生长因子 β (TGFβ) 刺激的反应性随着年龄的增长而增强。其次，老化的初始 CD4 T 细胞响应 T 细胞受体刺激而表现出改变的转录因子谱，包括 BATF 和 IRF4 表达增强以及 ID3 和 BCL6 表达减少。这些转录因子参与 TH9 分化以及 IL9 转录，表明转录因子谱中与衰老相关的变化有利于 TH9 定向。

更新日期：2019-07-01

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