Chromatin bound by survivin regulates the glycolytic switch in interferon-γ producing CD4+ T cells

2021 ◽  
Author(s):  
Malin Erlandsson ◽  
Karin Andersson ◽  
Nina Oparina ◽  
Venkataragavan Chandrasekaran ◽  
Anastasios Damdimopoulos ◽  
...  
Keyword(s):  
T Cells ◽  
Glucose Utilization ◽  
Interferon Γ ◽  
Interferon Regulatory Factor ◽  
Metabolic Adaptation ◽  
Regulatory Factor ◽  
Cell Functions ◽  
Interferon Regulatory Factor 1 ◽  
Direct Binding ◽  
Nuclear Survivin

Abstract Upon activation, CD4+ T cells adapt metabolically to fulfill their effector function in autoimmunity. Here we show that nuclear survivin is essential for transcriptional regulation of glucose utilization. We found that the glycolytic switch in interferon (IFN) g–producing CD4+ cells is dependent on a complex of survivin with interferon regulatory factor 1 (IRF1), and Smad3 and was reversed by survivin inhibition. Transcriptome analysis of CD4+ cells and sequencing of survivin-bound chromatin identified a hub of metabolism regulating genes whose transcription depended on survivin. Direct binding of survivin to IRF1 and SMAD3 promoted IRF1-mediated transcription, repressed SMAD3 activity, and lowered PFKFB3 production. Inhibiting survivin upregulated PFKFB3, restored glycolysis, and reduced glucose uptake, improving control over IFNg-dependent T-cell functions. Thus, IRF1-survivin-SMAD3 interactions are important for metabolic adaptation of CD4+ cells and provide an attractive strategy to counteract IFNg-dependent inflammation.

scholarly journals Interferon-γ Upregulates Expression of IFP35 Gene in HeLa Cells via Interferon Regulatory Factor-1

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e50932 ◽  
Author(s):  
Wei Yang ◽  
Juan Tan ◽  
Ruikang Liu ◽  
Xiaoxu Cui ◽  
Qinglin Ma ◽  
...  
Keyword(s):  
Hela Cells ◽  
Interferon Γ ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 1

scholarly journals 17β-Estradiol downregulates interferon regulatory factor-1 in murine splenocytes

2006 ◽  
Vol 37 (3) ◽  
pp. 421-432 ◽  
Author(s):  
Andrea J Lengi ◽  
Rebecca A Phillips ◽  
Ebru Karpuzoglu ◽  
Sattar Ansar Ahmed
Keyword(s):  
T Cells ◽  
Interferon Regulatory Factor ◽  
Lymphoid Cells ◽  
Regulatory Factor ◽  
Murine Splenocytes ◽  
Potent Inducer ◽  
Interferon Regulatory Factor 1 ◽  
17Β Estradiol ◽  
Ifn Γ ◽  
In Cells

Interferon regulatory factor-1 (IRF-1) is an important transcription factor that mediates interferon-γ (IFN-γ)-induced cell-signaling events. In this study, we examined whether 17β-estradiol alters IRF-1 in splenic lymphocytes, in view of the immunomodulatory effects of this natural female sex hormone including its ability to alter IFN-γ levels. We find that IRF-1 expression is markedly downregulated in splenocytes or purified T-cells from estrogen-treated mice at all time points studied when compared with their placebo counterparts. This decrease in IRF-1 in splenocytes from estrogen-treated mice is neither due to upregulation of IRF-1-interfering proteins (nucleophosmin or signal transducer and activator of transcription (STAT)-5) nor due to alternatively spliced IRF-1 mRNA. Given that IFN-γ is a potent inducer of IRF-1, direct addition of recombinant IFN-γ to splenocytes from either wild-type or IFN-γ-knockout mice, or the addition of recombinant IFN-γ to purified T-cells, was expected to stimulate IRF-1 expression. However, robust expression of IRF-1 in cells from estrogen-treated mice was not seen, unlike what was observed in cells from placebo-treated mice. Diminished IFN-γ induction of IRF-1 in cells from estrogen-treated mice was noticed despite comparable phosphorylated STAT-1 activation. These studies are the first to show that estrogen regulates IFN-γ-inducible IRF-1 in lymphoid cells, a finding that may have implications to IFN-γ-regulated immune and vascular diseases.

scholarly journals The Transcription Factor Interferon Regulatory Factor 1 (IRF-1) Is Important during the Maturation of Natural Killer 1.1+ T Cell Receptor–α/β+ (NK1+ T) Cells, Natural Killer Cells, and Intestinal Intraepithelial T Cells

1998 ◽  
Vol 187 (6) ◽  
pp. 967-972 ◽  
Author(s):  
Toshiaki Ohteki ◽  
Hiroki Yoshida ◽  
Toshifumi Matsuyama ◽  
Gordon S. Duncan ◽  
Tak W. Mak ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Lymphocyte Subsets ◽  
Cell Receptor ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 1

In contrast to conventional T cells, natural killer (NK) 1.1+ T cell receptor (TCR)-α/β+ (NK1+T) cells, NK cells, and intestinal intraepithelial lymphocytes (IELs) bearing CD8-α/α chains constitutively express the interleukin (IL)-2 receptor (R)β/15Rβ chain. Recent studies have indicated that IL-2Rβ/15Rβ chain is required for the development of these lymphocyte subsets, outlining the importance of IL-15. In this study, we investigated the development of these lymphocyte subsets in interferon regulatory factor 1–deficient (IRF-1−/−) mice. Surprisingly, all of these lymphocyte subsets were severely reduced in IRF-1−/− mice. Within CD8-α/α+ intestinal IEL subset, TCR-γ/δ+ cells and TCR-α/β+ cells were equally affected by IRF gene disruption. In contrast to intestinal TCR-γ/δ+ cells, thymic TCR-γ/δ+ cells developed normally in IRF-1−/− mice. Northern blot analysis further revealed that the induction of IL-15 messenger RNA was impaired in IRF-1−/− bone marrow cells, and the recovery of these lymphocyte subsets was observed when IRF-1−/− cells were cultured with IL-15 in vitro. These data indicate that IRF-1 regulates IL-15 gene expression, which may control the development of NK1+T cells, NK cells, and CD8-α/α+ IELs.

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