Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling
Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling
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DOI：
10.1038/s41590-019-0515-x
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发表时间：
2019-12-01
影响因子：
30.5
通讯作者：
Turley, Shannon J.
中科院分区：
文献类型：
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作者：
Brown, Flavian D.;Sen, Debattama R.;Turley, Shannon J.
淋巴结成纤维网状细胞（FRC）通过释放一氧化氮来响应来自活化的T细胞的信号，这抑制T细胞增殖并限制扩展的T细胞池的大小。与FRC的相互作用是否也支持活化的CD 8（+）T细胞的功能或分化尚不清楚。在这里，我们报告说，遇到FRC增强细胞因子的生产和重塑染色质的可及性，在新激活的CD 8（+）T细胞通过白细胞介素-6。这些表观遗传变化促进了代谢重编程，并通过差异转录因子活性放大了促生存途径的活性。因此，FRC预处理显著增强了病毒特异性CD 8（+）T细胞在体内的持久性，并增强了它们向组织驻留记忆T细胞的分化。我们的研究表明，FRC发挥的作用不仅限于限制T细胞的扩增，它们还可以塑造CD 8（+）T细胞的命运和功能。
Lymph node fibroblastic reticular cells (FRCs) respond to signals from activated T cells by releasing nitric oxide, which inhibits T cell proliferation and restricts the size of the expanding T cell pool. Whether interactions with FRCs also support the function or differentiation of activated CD8(+) T cells is not known. Here we report that encounters with FRCs enhanced cytokine production and remodeled chromatin accessibility in newly activated CD8(+) T cells via interleukin-6. These epigenetic changes facilitated metabolic reprogramming and amplified the activity of pro-survival pathways through differential transcription factor activity. Accordingly, FRC conditioning significantly enhanced the persistence of virus-specific CD8(+) T cells in vivo and augmented their differentiation into tissue-resident memory T cells. Our study demonstrates that FRCs play a role beyond restricting T cell expansion-they can also shape the fate and function of CD8(+) T cells.