The PI3K/AKT signaling pathway in regulatory T-cell development, stability, and function

Pompura, Saige L.; Dominguez‐Villar, Margarita

doi:10.1002/jlb.2mir0817-349r

Cited by 221 publications

(141 citation statements)

References 155 publications

(252 reference statements)

Supporting

Mentioning

133

Contrasting

Order By: Relevance

“…38 Meanwhile, SIRT2 deacetylates p65 to inhibit nuclear factor-jB (NF-jB) activity. 39 Because Akt and NF-jB are both important for Treg cell activity, [40][41][42][43] it is likely that up-regulation of SIRT2 influences Treg cell immunosuppressive function. However, because the exact role of Akt and NF-jB in Treg cell activity is still under debate, it is difficult to deduce the effect of SIRT2.…”

Section: Discussionmentioning

confidence: 99%

Sirtuin4 suppresses the anti‐neuroinflammatory activity of infiltrating regulatory T cells in the traumatically injured spinal cord

et al. 2019

View full text Add to dashboard Cite

Summary The neuroinflammation following traumatic spinal cord injury (SCI) is a critical process that impacts both the injury and the recovery of spinal cord parenchyma. Infiltrating regulatory T (Treg) cells are potent anti‐inflammatory cells that restrain post‐SCI neuroinflammation. To understand the molecular mechanisms underlying the activity of infiltrating Treg cells, we used a mouse spinal cord compression injury model to analyze the role of Sirtuins (SIRTs) in the modulation of infiltrating Treg cell functions. We found that the expressions of SIRT4 and SIRT6 were up‐regulated in infiltrating Treg cells. Using lentivirus‐mediated gene expression or RNA interference, we revealed that SIRT4 substantially inhibited the expression of Foxp3, interleukin‐10, and transforming growth factor‐β in Treg cells, whereas SIRT6 had little effect on Treg cells. Consistently, SIRT4 overexpression weakened the suppressive effect of Treg cells on lipopolysaccharide‐stimulated spinal cord CD11b+ myeloid cells. Knock‐down of SIRT4 enhanced the anti‐inflammatory activity of infiltrating Treg cells in the parenchyma of injured spinal cords. Additionally, SIRT4 overexpression blocked in vitro Treg cell generation from conventional T cells. Furthermore, SIRT4 down‐regulated 5′ AMP‐activated protein kinase (AMPK) signaling in Treg cells, whereas the AMPK agonist AICAR restored the expression of Foxp3 and interleukin‐10 in SIRT4‐overexpressing Treg cells. In conclusion, our research unveils a new mechanism by which the post‐SCI neuroinflammation is regulated.

show abstract

Section: Discussionmentioning

confidence: 99%

Sirtuin4 suppresses the anti‐neuroinflammatory activity of infiltrating regulatory T cells in the traumatically injured spinal cord

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Except the influence on immune system, supplementation of 30 g/kg fucoidan also decreased the transcription level of Ras that serves as a signalling switch controlling intracellular signalling networks (Wennerberg, Rossman, & Der, ). Nevertheless, fucoidan treatment increased the gene transcriptions of PI3K and AKT, which are the downstream molecular effectors of Ras signalling pathway and have important functions in controlling diverse cellular processes including cell growth, proliferation, differentiation, survival, autophagy and immune responses (Pompura & Dominguez‐Villar, ). Due to the critical functions of both PI3K/AKT and Ras signalling pathways, future studies are required to elucidate the mechanism and consequence of the changed expression level of Ras, PI3K and AKT in the intestine of gibel carp in response to fucoidan treatment.…”

Section: Discussionmentioning

confidence: 99%

Effects of a highly purified fucoidan fromUndaria pinnatifidaon growth performance and intestine health status of gibel carpCarassius auratus gibelio

et al. 2019

View full text Add to dashboard Cite

A six‐week feeding trial was conducted to determine the effects of different concentrations of fucoidan (1 g/kg, 10 g/kg and 30 g/kg; w/w) from Undaria pinnatifida on gibel carp (Carassius auratus gibelio). Our results demonstrated that 30 g/kg fucoidan significantly increased (p < .05) growth performance, intestinal digestive enzyme activities, acid phosphatase activity and immunoglobulin M content. Histological examinations revealed that gibel carp receiving 30 g/kg fucoidan had significant higher abundance of mucin‐containing goblet cells in middle and distal intestine as compared with control treatment (p < .05). Intestinal microbiota analysis showed that 30 g/kg fucoidan supplementation significantly increased (p < .05) the abundance of Cetobacterium and Aeromonas, but lowered (p < .05) the prevalence of pathogenic bacteria Plesiomonas and a mucin‐degrading bacterium Mucinivorans. Furthermore, RNA‐seq and RT‐qPCR analysis indicated that 30 g/kg fucoidan caused significant changes (p < .05) in the expression of genes involved in immune regulation (such as interleukin‐8 and cyclooxygenase), signal transduction (such as phosphatidylinositol‐4,5‐bisphosphate 3‐kinase and protein kinase B) and nutrition utilization (maltase–glucoamylase and muscarinic acetylcholine receptor 3). Together, the current study shows that fucoidan supplementation could elevate the activity of intestinal digestive enzymes, modulate intestinal microbial communities and potentiate a higher state of immune readiness, which might consequently improve growth performance and intestine health status of gibel carp.

show abstract

“…PI3K/Akt pathway is particularly vital with regard to mediating survival signals in a wide range of ways (Yang, Yan, Li, & Zhang, ). Findings obtained from a study showed that the PI3K/Akt signaling pathway is an imperative node controlling cell growth, migration, proliferation, and metabolism in mammalian cells (Pompura, & Dominguez‐Villar, ). A study demonstrated that inhibiting the expression of ANXA3 significantly reduced the proliferation, migration, and invasion of breast cancer cells, thus inducing cell apoptosis and inhibiting cell proliferation, migration, and invasion (T. Zhou et al, ).…”

Section: Discussionmentioning

confidence: 99%

Annexin A3 gene silencing promotes myocardial cell repair through activation of the PI3K/Akt signaling pathway in rats with acute myocardial infarction

Meng

Zhang

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Acute myocardial infarction (AMI), as a severe consequence of coronary atherosclerotic heart disease, always contributes to the loss of myocardial cells. Mounting evidence shows that annexin protects the myocardium from ischemic injury. In this study, we examine the inhibition of annexin A3 (ANXA3) on AMI through the phosphatidylinositide 3‐kinase/protein kinase B (PI3K/Akt) signaling pathway. We selected rats to build an AMI model which was then assigned into different groups. The hemodynamic parameters after transfection were detected by using enzyme‐linked immunosorbent assay. The effect of silencing of ANXA3 on inflammatory reaction and the PI3K/Akt signaling pathway was assessed. Rats transfected with ANXA3‐short hairpin RNA had alleviated hemodynamics, inflammatory reaction, decreased infarct size, α‐smooth muscle actin, Collagen I, and Collagen III as well as an increased vascular endothelial growth factor. Silencing ANAX3 would promote repair and healing of myocardial tissue by activation of the PI3K/Akt signaling pathway. Collectively, our study provides evidence that the downregulation of ANXA3 promotes the repair and healing of myocardial tissues by activating the PI3K/Akt signaling pathway.

show abstract

The PI3K/AKT signaling pathway in regulatory T-cell development, stability, and function

Cited by 221 publications

References 155 publications

Sirtuin4 suppresses the anti‐neuroinflammatory activity of infiltrating regulatory T cells in the traumatically injured spinal cord

Sirtuin4 suppresses the anti‐neuroinflammatory activity of infiltrating regulatory T cells in the traumatically injured spinal cord

Effects of a highly purified fucoidan fromUndaria pinnatifidaon growth performance and intestine health status of gibel carpCarassius auratus gibelio

Annexin A3 gene silencing promotes myocardial cell repair through activation of the PI3K/Akt signaling pathway in rats with acute myocardial infarction

Contact Info

Product

Resources

About