1. Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling
- Author
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Kevin Bi, Jernej Godec, Arlene H. Sharpe, Frank A. Schildberg, Illana A. Stanley, Debattama R. Sen, Flavian D. Brown, Veronika Lukacs-Kornek, Stéphane J. H. Ricoult, Varun N. Kapoor, Nika N. Danial, W. Nicholas Haining, Viviana Cremasco, Brendan D. Manning, Kathleen B. Yates, Shannon J. Turley, Justin D. Trombley, Martin W. LaFleur, and Hye-Jung Kim
- Subjects
Cytotoxicity, Immunologic ,0301 basic medicine ,Cell Survival ,Cellular differentiation ,medicine.medical_treatment ,T cell ,Immunology ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,Nitric Oxide ,Article ,Epigenesis, Genetic ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Reticular cell ,medicine ,Animals ,Immunology and Allergy ,Lymph node ,Cells, Cultured ,Cell Proliferation ,Mice, Knockout ,Interleukin-6 ,Cell growth ,Chemistry ,Cell Differentiation ,Fibroblasts ,Cellular Reprogramming ,Chromatin Assembly and Disassembly ,Chromatin ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Cytokine ,Gene Expression Regulation ,Lymph Nodes ,Immunologic Memory ,CD8 ,030215 immunology - 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.
- Published
- 2019