학술논문
Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling
Document Type
Academic Journal
Author
Source
Nature Immunology. December 2019, Vol. 20 Issue 12, p1668, 13 p.
Subject
Language
English
ISSN
1529-2908
Abstract
Author(s): Flavian D. Brown [sup.1] [sup.2] [sup.3] [sup.4] [sup.5] [sup.13], Debattama R. Sen [sup.1] [sup.2], Martin W. LaFleur [sup.1] [sup.2] [sup.3] [sup.4], Jernej Godec [sup.1] [sup.2] [sup.3] [sup.4], Veronika Lukacs-Kornek [...]
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.sup.+ T cells is not known. Here we report that encounters with FRCs enhanced cytokine production and remodeled chromatin accessibility in newly activated CD8.sup.+ 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.sup.+ 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.sup.+ 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.
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.sup.+ T cells is not known. Here we report that encounters with FRCs enhanced cytokine production and remodeled chromatin accessibility in newly activated CD8.sup.+ 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.sup.+ 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.sup.+ 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.