Skip to main content

Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling.

Nature immunology

Authors: 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

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.

PMID: 31636464

Participating cluster members