T Cell Receptor and Cytokine Signaling Can Function at Different Stages to Establish and Maintain Transcriptional Memory and Enable T Helper Cell Differentiation.
T Cell Receptor and Cytokine Signaling Can Function at Different Stages to Establish and Maintain Transcriptional Memory and Enable T Helper Cell Differentiation.
复制标题
DOI：
10.3389/fimmu.2017.00204
复制
发表时间：
2017
影响因子：
7.3
通讯作者：
Cockerill PN
中科院分区：
文献类型：
--
作者：
Bevington SL;Cauchy P;Withers DR;Lane PJ;Cockerill PN
经验T细胞通过快速回忆反应表现出免疫记忆，对再刺激的反应比naïve T细胞快得多。免疫记忆的形成始于最初的缓慢反应，此时naïve T细胞转变为增殖的T母细胞，诱导免疫反应基因被重新编程为活性染色质结构域。我们证明了这些活性结构域是由数千个启动元件支持的，这些启动元件与可诱导的转录增强子合作，使对刺激的有效反应成为可能。在这种反应结束时，这些细胞中有一小部分作为长期记忆T细胞返回到静止状态。我们提出，启动因子可以在肇事逃逸过程中建立，依赖于诱导因子AP-1，但随后由构成因子RUNX1和ETS-1维持。这种启动机制也可能使基因接受在极化条件下遇到的其他分化诱导因子，如GATA3和TBX21。最近激活的T细胞的增殖和静止记忆T细胞免疫记忆的维持也依赖于AP-1上游的各种细胞因子信号通路。我们认为免疫记忆是由T细胞受体信号传导建立的，但由细胞因子信号传导维持。
Experienced T cells exhibit immunological memory via a rapid recall response, responding to restimulation much faster than naïve T cells. The formation of immunological memory starts during an initial slow response, when naïve T cells become transformed to proliferating T blast cells, and inducible immune response genes are reprogrammed as active chromatin domains. We demonstrated that these active domains are supported by thousands of priming elements which cooperate with inducible transcriptional enhancers to enable efficient responses to stimuli. At the conclusion of this response, a small proportion of these cells return to the quiescent state as long-term memory T cells. We proposed that priming elements can be established in a hit-and-run process dependent on the inducible factor AP-1, but then maintained by the constitutive factors RUNX1 and ETS-1. This priming mechanism may also function to render genes receptive to additional differentiation-inducing factors such as GATA3 and TBX21 that are encountered under polarizing conditions. The proliferation of recently activated T cells and the maintenance of immunological memory in quiescent memory T cells are also dependent on various cytokine signaling pathways upstream of AP-1. We suggest that immunological memory is established by T cell receptor signaling, but maintained by cytokine signaling.
在人14q32.1处的大型组蛋白高乙酰化的大型复杂结构域的形成需要Serpin基因座控制区域。
影响因子：
14.9
作者：
Baxter, EW;Cummings, WJ;Fournier, REK
通讯作者：
Fournier, REK