Journal Article

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

Godec, Jernej, Cremasco, Viviana, Lukacs-Kornek, Veronika, Sharpe, Arlene H., Kim, Hye-Jung, Trombley, Justin D., Turley, Shannon J., Stanley, Illana A., Danial, Nika N., Yates, Kathleen B., LaFleur, Martin W., Haining, W. Nicholas, Manning, Brendan D., Brown, Flavian D., Bi, Kevin, Ricoult, Stéphane J. H., Kapoor, Varun N., Sen, Debattama R., Schildberg, Frank A.

2019

Overview

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. Fibroblastic reticular cells (FRCs) are dynamic regulators of lymphoid tissue structure. Turley and colleagues show FRCs also support activated T cells by producing IL-6, which confers an advantage to CD8+ T cell memory responses.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/1647 / 631/250 / Animals / Biomedical and Life Sciences / Biomedicine / CD8 antigen / CD8-Positive T-Lymphocytes - immunology / Cell Differentiation / Cell Proliferation / Cell Survival / Cells, Cultured / Cellular Reprogramming / Chromatin / Chromatin Assembly and Disassembly / Cytotoxicity, Immunologic / Epigenesis, Genetic / Epigenetic inheritance / Epigenetics / Fibroblasts - physiology / Gene Expression Regulation / Immunologic Memory / Immunological memory / Immunology / Infectious Diseases / Interleukin 6 / Interleukin-6 - genetics / Interleukin-6 - metabolism / Interleukins / Lymph nodes / Lymph Nodes - immunology / Lymphocyte Activation / Lymphocytes / Lymphocytes T / Lymphoid tissue / Memory cells / Mice / Mice, Inbred C57BL / Mice, Knockout / Nitric oxide / Nitric Oxide - metabolism / T cells