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Nat Immunol DOI:10.1038/s41590-019-0515-x

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

Publication TypeJournal Article
Year of Publication2019
AuthorsBrown, FD, Sen, DR, LaFleur, MW, Godec, J, Lukacs-Kornek, V, Schildberg, FA, Kim, H-J, Yates, KB, Ricoult, SJH, Bi, K, Trombley, JD, Kapoor, VN, Stanley, IA, Cremasco, V, Danial, NN, Manning, BD, Sharpe, AH, W Haining, N, Turley, SJ
JournalNat Immunol
Date Published2019 Dec

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.


Alternate JournalNat. Immunol.
PubMed ID31636464