成纤维细胞网状细胞促进T细胞代谢与存活
作者：小柯机器人 发布时间：2019/10/22 16:14:05
美国丹娜法伯癌症研究所Shannon J. Turley、W. Nicholas Haining以及哈佛医学院Arlene H. Sharpe等研究人员合作发现，成纤维细胞网状细胞（FRC）通过表观遗传重塑促进T细胞的代谢与存活。相关论文在线发表于2019年10月21日的《自然—免疫学》。
研究人员发现，与FRC的接触增强了细胞因子的产生，并通过白介素6在新激活的CD8阳性 T细胞中重塑了染色质的可及性。这些表观遗传学变化促进了代谢重编程，并通过差异转录因子的活性放大了生存途径的活性。因此，FRC的调控显著增强了病毒特异性CD8阳性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。
这项研究表明，FRC的作用不仅限于限制T细胞扩增，它们还可以影响CD8阳性T细胞的命运和功能。
据介绍，淋巴结FRC通过释放一氧化氮来响应活化T细胞的信号，这抑制T细胞增殖并限制了扩增的T细胞池的大小。与FRC的相互作用是否还支持活化的CD8 阳性T细胞的功能或分化尚不清楚。
附：英文原文
Title:Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling
Author:Flavian D. Brown, Debattama R. Sen, Martin W. LaFleur, Jernej Godec, Veronika Lukacs-Kornek, Frank A. Schildberg, Hye-Jung Kim, Kathleen B. Yates, Stéphane J. H. Ricoult, Kevin Bi, Justin D. Trombley, Varun N. Kapoor, Illana A. Stanley, Viviana Cremasco, Nika N. Danial, Brendan D. Manning, Arlene H. Sharpe, W. Nicholas Haining & Shannon J. Turley
Issue&Volume:21 October 2019
Abstract:
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.
DOI:10.1038/s41590-019-0515-x
期刊信息
Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：23.53
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex