Oscillatory mTOR inhibition and Treg increase in kidney transplantation

Sabbatini, Massimo; Ruggiero, Giuseppina; Palatucci, Anna Teresa; Rubino, Valentina; Federico, Stefano; Giovazzino, Angela; Apicella, Luca; Santopaolo, Marianna; Matarese, Giuseppe; Galgani, Mario; Terrazzano, Giuseppe

doi:10.1111/cei.12669

Cited by 27 publications

(21 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…; Sabbatini et al. ), and the present results are not consistent with these reports. Everolimus might not greatly influence renal pathology, and our results suggest a need for further analyses.…”

Section: Discussioncontrasting

confidence: 99%

“…In contrast, urinary protein levels, the glomerulosclerosis index (GSI), and tubulointerstitial injury score (TIS) were not changed and renal inflammation was inhibited by administration of everolimus. Everolimus has been used as a growth inhibitor for kidney cancer and as an immunosuppressant for renal transplant in clinical practice (Sabbatini et al 2015). Side effects such as a decline in renal function by this drug have not been reported Sabbatini et al 2015), and the present results are not consistent with these reports.…”

Section: Discussioncontrasting

confidence: 83%

“…Everolimus has been used as a growth inhibitor for kidney cancer and as an immunosuppressant for renal transplant in clinical practice (Sabbatini et al 2015). Side effects such as a decline in renal function by this drug have not been reported Sabbatini et al 2015), and the present results are not consistent with these reports. Everolimus might not greatly influence renal pathology, and our results suggest a need for further analyses.…”

Section: Discussioncontrasting

confidence: 83%

“…Everolimus has been used as a growth inhibitor for kidney cancer and as an immunosuppressant for renal transplant in clinical practice (Sabbatini et al. ). Side effects such as a decline in renal function by this drug have not been reported (Takahashi et al.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Effects of mTOR inhibition on cardiac and adipose tissue pathology and glucose metabolism in rats with metabolic syndrome

Uchinaka

Yoneda

Yamada

et al. 2017

Pharmacology Res & Perspec

View full text Add to dashboard Cite

The mammalian target of rapamycin (mTOR) is a regulator of metabolism and is implicated in pathological conditions such as obesity and diabetes. We aimed to investigate the role of mTOR in obesity. A new animal model of metabolic syndrome (MetS), named DahlS.Z‐Lepr fa/Lepr fa (DS/obese) rats was established previously in our laboratory. In this study, we used this model to evaluate the effects of mTOR inhibition on cardiac and adipose tissue pathology and glucose metabolism. DS/obese rats were treated with the mTOR inhibitor, everolimus, (0.83 mg/kg per day, per os) for 4 weeks at 9 weeks of age. Age‐matched homozygous lean (DahlS.Z‐Lepr +/Lepr + or DS/lean) littermates of DS/obese rats were used as controls. Treatment with everolimus ameliorated hypertension, left ventricular (LV) hypertrophy and fibrosis, and LV diastolic dysfunction, and attenuated cardiac oxidative stress and inflammation in DS/obese rats, but had no effect on these parameters in DS/lean rats. Treatment with everolimus reduced Akt Thr308 phosphorylation in the heart of DS/obese rats. It also alleviated obesity, hyperphagia, adipocyte hypertrophy, and adipose tissue inflammation in DS/obese rats. Everolimus treatment exacerbated glucose intolerance, but did not affect Akt phosphorylation levels in the fat or liver in these rats. Pancreatic β‐cell mass was increased in DS/obese rats compared with that in DS/lean rats and this effect was attenuated by everolimus. Activation of mTOR signaling contributes to the pathophysiology of MetS and its associated complications. And mTOR inhibition with everolimus ameliorated obesity as well as cardiac and adipose tissue pathology, but exacerbated glucose metabolism in rats with MetS.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 83%

Section: Discussioncontrasting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of mTOR inhibition on cardiac and adipose tissue pathology and glucose metabolism in rats with metabolic syndrome

Uchinaka

Yoneda

Yamada

et al. 2017

Pharmacology Res & Perspec

View full text Add to dashboard Cite

show abstract

“…We reported the possibility that this phenomenon could be due to the fact that to enter the cell cycle, Treg cells need low mTOR phosphorylation (achieved with rapamycin treatment) and after entering the cell cycle, IL-2 can help to reactivate mTOR which is necessary for Treg cells to proliferate over time. This “oscillatory” phenomenon for Treg cell expansion would occur both in vitro and in vivo (20, 7, 4, 44). …”

Section: Effects Of Metabolism On Foxp3 Expressionmentioning

confidence: 99%

Role of Metabolism in the Immunobiology of Regulatory T Cells

Galgani

Rosa

Cava

et al. 2016

The Journal of Immunology

100

View full text Add to dashboard Cite

Intracellular metabolism is central to cell activity and function. CD4+CD25+ regulatory T cells (Tregs) that express the transcription factor FOXP3 play a pivotal role in the maintenance of immune tolerance to self. Recent studies showed that the metabolism and function of Tregs are influenced significantly by local environmental conditions and the availability of certain metabolites. It also was reported that defined metabolic programs associate with Treg differentiation, expression of FOXP3, and phenotype stabilization. This article reviews how metabolism modulates FOXP3 expression and Treg function, what environmental factors are involved, and how metabolic manipulation could alter Treg frequency and function in physiopathologic conditions.

show abstract

Targeting regulatory T cell metabolism in disease: Novel therapeutic opportunities

2023

View full text Add to dashboard Cite

Regulatory T cells (Tregs) are essential for immune homeostasis and suppression of pathological autoimmunity but can also play a detrimental role in cancer progression via inhibition of anti‐tumor immunity. Thus, there is broad applicability for therapeutic Treg targeting, either to enhance function, for example, through adoptive cell therapy (ACT), or to inhibit function with small molecules or antibody‐mediated blockade. For both of these strategies, the metabolic state of Tregs is an important consideration since cellular metabolism is intricately linked to function. Mounting evidence has shown that targeting metabolic pathways can selectively promote or inhibit Treg function. This review aims to synthesize the current understanding of Treg metabolism and discuss emerging metabolic targeting strategies in the contexts of transplantation, autoimmunity, and cancer. We discuss approaches to gene editing and cell culture to manipulate Treg metabolism during ex vivo expansion for ACT, as well as in vivo nutritional and pharmacological interventions to modulate Treg metabolism in disease states. Overall, the intricate connection between metabolism and phenotype presents a powerful opportunity to therapeutically tune Treg function.

show abstract

Oscillatory mTOR inhibition and Treg increase in kidney transplantation

Cited by 27 publications

References 51 publications

Effects of mTOR inhibition on cardiac and adipose tissue pathology and glucose metabolism in rats with metabolic syndrome

Effects of mTOR inhibition on cardiac and adipose tissue pathology and glucose metabolism in rats with metabolic syndrome

Role of Metabolism in the Immunobiology of Regulatory T Cells

Targeting regulatory T cell metabolism in disease: Novel therapeutic opportunities

Contact Info

Product

Resources

About