| Literature DB >> 31636464 |
Flavian D Brown1,2,3,4,5,6, Debattama R Sen1,2, Martin W LaFleur1,2,3,4, Jernej Godec1,2,3,4, Veronika Lukacs-Kornek5,7, Frank A Schildberg3,4,5,8, Hye-Jung Kim3,5, Kathleen B Yates2,9, Stéphane J H Ricoult10, Kevin Bi2,9, Justin D Trombley3,4, Varun N Kapoor11, Illana A Stanley12,13, Viviana Cremasco5,14, Nika N Danial12,13, Brendan D Manning10, Arlene H Sharpe15,16,17,18, W Nicholas Haining19,20,21,22, Shannon J Turley23,24.
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.Entities:
Mesh：
Substances：
Year: 2019 PMID： 31636464 PMCID： PMC7464610 DOI： 10.1038/s41590-019-0515-x
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606