Intercellular interplay between Sirt1 signalling and cell metabolism in immune cell biology

Chen, Xi; Lu, Yun; Zhang, Zhengguo; Wang, Jian; Yang, Hui; Liu, Guangwei

doi:10.1111/imm.12473

Cited by 76 publications

(57 citation statements)

References 158 publications

(376 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, SIRT1 acts to dampen T cell activity and its absence is associated with increased inflammation and autoimmunity (20, 26). In contrast to the role of SIRT1 in T cells, we demonstrate here that SIRT3 augments T cell activation, proliferation, but did not substantially affect cytokine production in response to non-specific TCR signaling or an allogeneic stimulus in vitro .…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Deacetylase SIRT3 Plays an Important Role in Donor T Cell Responses after Experimental Allogeneic Hematopoietic Transplantation

Toubai

Tamaki

Peltier

et al. 2018

The Journal of Immunology

View full text Add to dashboard Cite

Allogeneic stem cell transplantation (allo-HCT) through its graft-versus-tumor (GVT) effects is a curative therapy against many hematological malignancies. However, GVT is linked to harmful graft-versus-host disease (GVHD) after allo-HCT. Both GVT and GVHD require allogeneic T cell responses, which is an energetically costly process that causes oxidative stress. Sirtuin 3 (SIRT3), a mitochondrial histone deacetylases (HDAC), plays an important role in cellular processes through inhibition of reactive oxygen species (ROS). Non-mitochondrial class of HDACs regulate T cell responses; but the role of mitochondrial HDACs, specifically SIRT3, on donor T cell responses after allo-HCT remain unknown. Herein we report that SIRT3 deficient (SIRT3-/-) donor T cells cause reduced GVHD severity in multiple clinically relevant murine models. The GVHD protective effect of allogeneic SIRT3-/- T cells was associated with a reduction in their activation, reduced CXCR3 expression, and no significant impact on cytokine secretion or cytotoxic functions. Intriguingly, the GVHD protective effect of SIRT3-/- T cells was associated with a reduction in ROS production which is contrary to the effect of SIRT3 deficiency on ROS production in other cells/tissues and likely a consequence of their deficient activation. Notably the reduction in GVHD in the gastrointestinal (GI) tract was not associated with a substantial reduction in the graft-versus-tumor (GVT) effect. Collectively these data reveal that SIRT3 activity promotes allogeneic donor T cell responses and ROS production without altering T cell cytokine or cytolytic functions and identify SIRT3 as a novel target on donor T cells to improve outcomes after allo-HCT.

show abstract

Section: Discussionmentioning

confidence: 99%

Mitochondrial Deacetylase SIRT3 Plays an Important Role in Donor T Cell Responses after Experimental Allogeneic Hematopoietic Transplantation

Toubai

Tamaki

Peltier

et al. 2018

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In OVA-sensitized and challenged mice, Ichikawa et al found that the expression of SIRT1 mRNA in the lungs was decreased when compared with that in control mice [5]. Moreover, they found that treatment of OVA mice with a SIRT1 activator decreased inflammatory cell lung infiltrates and IL-5 and IL-13 levels in the BAL fluid compared to those in the vehicle treatment [6] , which indicated the anti-inflammation effects of SIRT1. In addition, Wang et al also confirmed decreased SIRT1 expression in the lung tissues of OVA mice [7].…”

Section: Introductionmentioning

confidence: 99%

Suppression of Sirtuin-1 Increases IL-6 Expression by Activation of the Akt Pathway During Allergic Asthma

Tang

Chen

Meng

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: A growing number of studies have demonstrated that the activity and expression level of sirtuin-1 (SIRT1) are decreased in asthma patients; however, the mechanisms underlying decreased SIRT1 expression and function are still not completely understood. Interleukin (IL)-6 plays important roles in inflammation during allergic asthma. In this study, we examined whether loss of SIRT1 activity regulated the expression of IL-6 and further verified the underlying mechanisms. Methods: The human airway epithelial cell line 16HBE was used to test the effects of the SIRT1 inhibitor (salermide) on expression of IL-6. IL-6 mRNA and protein expression were assessed with real-time polymerase chain reaction (PCR), immunochemistry, and ELISA. OVA-challenged mice were used as an asthma model to investigate the effect of SIRT1 activation on IL-6 and relative Akt phosphorylation level. Results: We found that inhibition of SIRT1 increased IL-6 mRNA and protein levels in a time-dependent manner, which was accompanied by increased Akt pathway activation in 16HBE cells. Furthermore activation of Akt showed upregulated expression of the IL-6 protein whereas Akt inhibitor, LY294002 or Akt siRNA significantly inhibited SIRT1-regulated IL-6 expression. Conversely, activation of SIRT1 inhibited Akt activation and IL-6 expression in an asthmatic mice model and 16HBE cells. Conclusion: Our results indicate the potential role of SIRT1 in regulating inflammation by modulation of IL-6 expression in an Akt-dependent manner during allergic asthma.

show abstract

“…Caffeine is important to reduce inflammatory processes [99,100] with adipose tissue transformation and release of inflammatory cytokines that induce NAFLD [100]. Sirt 1 is involved in autoimmunity [101,102] with relevance to regulation of various immune cell events in the adipose tissue and liver.…”

Section: Defective Adipose Tissue-liver Crosstalk In the Induction Ofmentioning

confidence: 99%

Caffeine with Links to NAFLD and Accelerated Brain Aging

Martins¹

2018

Non-Alcoholic Fatty Liver Disease - Molecular Bases, Prevention and Treatment

View full text Add to dashboard Cite

Nutritional diets are essential to prevent nonalcoholic fatty liver disease (NAFLD) in the global obesity and diabetes epidemic. The ingestion of palmitic acid-rich diets induces NAFLD in animal and human studies. The beneficial properties of olive oil (oleic acid) may be superseded by ingestion of palmitic acid-rich diets. Hepatic caffeine metabolism is regulated by palmitic and oleic acid with effects of these fats on amyloid beta metabolism. Healthy fats such as olive oil may facilitate rapid amyloid beta clearance in the periphery to maintain drug therapy in diabetes and various neurological diseases. Repression of the anti-aging gene sirtuin 1 (Sirt 1) prevents the beneficial properties of olive oil. Brain disorders induce NAFLD and supersede caffeine's therapeutic effects in the prevention of NAFLD. Delayed hepatic caffeine metabolism in NAFLD and increased caffeine transport to the brain with aging-induced mitophagy in neurons with induction of type 3 diabetes and neurodegenerative disease.

show abstract

Intercellular interplay between Sirt1 signalling and cell metabolism in immune cell biology

Cited by 76 publications

References 158 publications

Mitochondrial Deacetylase SIRT3 Plays an Important Role in Donor T Cell Responses after Experimental Allogeneic Hematopoietic Transplantation

Mitochondrial Deacetylase SIRT3 Plays an Important Role in Donor T Cell Responses after Experimental Allogeneic Hematopoietic Transplantation

Suppression of Sirtuin-1 Increases IL-6 Expression by Activation of the Akt Pathway During Allergic Asthma

Caffeine with Links to NAFLD and Accelerated Brain Aging

Contact Info

Product

Resources

About