Rapamycin Modulate Treg/Th17 Balance via Regulating Metabolic Pathways: A Study in Mice.

Abstract:

:A regulatory T (Treg) cell/T helper 17 (Th17) cell imbalance is involved in many autoimmune diseases. Rapamycin (Rapa), a clinically used immunosuppressive drug, has been shown to inhibit Th17 cell differentiation but promote Treg cell generation. In this study, we aimed to study the mechanism of Rapa acting on Treg and Th17 cell differentiation. Purified mouse CD4+CD25- T cells were stimulated and polarized in vitro to generate Th17 or Treg cells in the presence or absence of Rapa. We first confirmed that Rapa inhibited the differentiation of Th17 cells and greatly promoted Treg cell generation in vitro. As metabolic pathways play a key role in T cell differentiation, we then detected the metabolic programs in Rapa-treated T cells. We found that Rapa blocked glycolysis in induced Th17 cells, evidenced by reduced glucose uptake, and inhibited expression of glucose transporter 1 and the rate-limiting enzyme HK2. In addition, the expression of c-Myc and of HIF-1α transcription factor, which regulate many genes involved in glycolysis, were inhibited by Rapa. Conversely, Rapa promoted fatty acid oxidation (FAO) metabolism in differentiated Treg cells, with the elevation of FAO product β-hydroxybutyrate, and increased expression of ATGL and CPT1A, the key enzymes of FAO in differentiated Treg cells. The expression of phospho-AMPKα, the key signal in the regulation of FAO, was also promoted in Rapa-treated induced Treg cells. Together, these findings indicated that Rapa abrogated glycolysis in Th17 cells but facilitated FAO in induced Treg cells, which may underlie the mechanism by which Rapa regulates the Treg/Th17 balance.

journal_name

Transplant Proc

authors

Zhang J,Jin H,Xu Y,Shan J

doi

10.1016/j.transproceed.2019.04.067

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

2136-2140

issue

6

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(18)31633-6

journal_volume

51

pub_type

杂志文章
  • Artificial islets from hybrid spheroids of three pancreatic cell lines.

    abstract::Pancreatic islets have been the focus of recent studies exploring the pathologic mechanisms of diabetes mellitus as well as more effective and radical treatments for this disease. Islet transplantation is a promising therapeutic strategy; however, isolation of pancreatic islets for this purpose has been challenging, b...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2013.11.074

    authors: Jo YH,Jang IJ,Nemeno JG,Lee S,Kim BY,Nam BM,Yang W,Lee KM,Kim H,Takebe T,Kim YS,Lee JI

    更新日期:2014-05-01 00:00:00

  • Conversion to everolimus in liver transplant patients with renal dysfunction.

    abstract::Calcineurin inhibitor (CNI) immunosuppressive therapy post-liver transplantation (OLT) is important to reduce graft rejection episodes. However, these drugs show important side effects, particularly renal dysfunction (RDF). Changing from CNI to a nonnephrotoxic drug, as mammalian target of rapamycin (mTOR) inhibitor m...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2011.06.009

    authors: Pérez T,Segovia R,Castro L,Roblero JP,Estela R

    更新日期:2011-07-01 00:00:00

  • Triple therapy using direct-acting agents for recurrent hepatitis C after liver transplantation: a single-center experience.

    abstract:BACKGROUND:Hepatitis C viral graft reinfection is almost a universal event after liver transplantation with consequent disease progression. METHODS:We applied triple therapy (n = 21) with the use of telaprevir (TVR; n = 12) or simeprevir (SVR; n = 9). RESULTS:TVR was given at the dose 1,500 mg daily (n = 11) with red...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2014.10.058

    authors: Ikegami T,Yoshizumi T,Soejima Y,Harimoto N,Itoh S,Takeishi K,Uchiyama H,Kawanaka H,Yamashita YI,Tsujita E,Harada N,Oki E,Saeki H,Kimura Y,Shirabe K,Maehara Y

    更新日期:2015-04-01 00:00:00

  • Cerebral blood flow in fulminant hepatitis.

    abstract::Fulminant hepatic failure (FHF) is often complicated with cerebral edema, intracranial hypertension, and coma. Cytotoxic and vasogenic factors have been recognized in the etiology of cerebral edema. One of the main causes seems to be the accumulation of glutamine in astrocytes, which is produced from ammonia and the e...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2006.01.040

    authors: Feltracco P,Serra E,Barbieri S,Tiberio I,Rizzi S,Salvaterra F

    更新日期:2006-04-01 00:00:00

  • Teenagers in Rural Areas Faced With Organ Donation and Transplantation.

    abstract:INTRODUCTION:In rural areas it is common to find unfavorable attitudes toward organ donation, and therefore it is important to find out the attitude and profile of new generations for improving predisposition to organ donation in these areas. Our objective was to analyze the attitude toward organ donation and the relat...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2017.09.054

    authors: Febrero B,Almela J,Ríos A,Ros I,Pérez-Sánchez B,Martínez-Alarcón L,Ruiz-Carreño P,Ferreras D,Ramírez P,Parrilla P

    更新日期:2018-03-01 00:00:00

  • Liver transplantation for acute liver failure: the Hungarian experience.

    abstract::Acute liver failure (ALF) counts for 9%-11% of activity in leading liver transplant programs. We have summarized the Hungarian Liver Transplant Program experience for ALF among 412 consecutive orthotopic liver transplantations (OLTs). All OLTs were performed without an extended international donor background. The prop...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2011.03.076

    authors: Nemes B,Zádori G,Görög D,Fehérvári I,Kóbori L,Langer RM

    更新日期:2011-05-01 00:00:00

  • Factors Associated With the Willingness of Clinical Health Care Professionals for Living Organ Donation.

    abstract::Understanding the attitudes and willingness in regard to living organ donation of health care professionals is important for clinical practice and needs to be addressed. Thus, the objective of this study was to examine willingness and its influencing factors in regard to living organ donation in clinical health care p...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2018.02.179

    authors: Lin MM,Hsu YN,Wang YW,Weng LC,Chin YF

    更新日期:2018-10-01 00:00:00

  • Endothelial dysfunction in peritoneal dialysis patients with and without failed renal transplants.

    abstract:BACKGROUND:Endothelial dysfunction (ED) is a common, early abnormality that predisposes patients to develop atherosclerosis and cardiovascular events; inflammation is associated with atherosclerosis and malnutrition. Patients with failed transplants are usually complicated by inflammation; however, ED in this group of ...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2009.06.200

    authors: Gorgulu N,Yelken B,Caliskan Y,Elitok A,Cimen O,Yazici H,Oflaz H,Turkmen A,Bozfakioglu S,Sever MS

    更新日期:2009-11-01 00:00:00

  • Alpha-interferon with ribavirin in the treatment of hemodialysis patients with hepatitis C.

    abstract:INTRODUCTION:Hepatitis C Viral (HCV) infection is the leading cause of chronic liver disease in end-stage renal disease patients (ESRD). The impact of HCV on patient and graft survival posttransplantation is controversial. The most successful approach is to eliminate the virus while the patient is on dialysis prior to ...

    journal_title:Transplantation proceedings

    pub_type: 临床试验,杂志文章

    doi:10.1016/j.transproceed.2004.07.025

    authors: Mousa DH,Abdalla AH,Al-Shoail G,Al-Sulaiman MH,Al-Hawas FA,Al-Khader AA

    更新日期:2004-07-01 00:00:00

  • Prevalence and manifestations of tuberculosis in renal transplant recipients: a single-center experience in Thailand.

    abstract::This retrospective review presented the prevalence and manifestations of tuberculosis among renal transplant recipients in our center between 1987 and mid 2007. The prevalence of tuberculosis was 5/151 (3.3%) recipients with a median age of 49 years (range = 38-55). The median time of diagnosis after transplantation w...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2008.06.020

    authors: Ruangkanchanasetr P,Natejumnong C,Kitpanich S,Chaiprasert A,Luesutthiviboon L,Supaporn T

    更新日期:2008-09-01 00:00:00

  • Donor-recipient age difference and graft survival in living donor kidney transplantation.

    abstract:BACKGROUND:In paired living kidney exchange donation from an old donor to a young recipient, it may be argued that elderly donors provide an inferior quality kidney. However, the impact of donors older than recipients on transplant outcomes remains unclear. METHODS:We retrospectively reviewed the charts of primary liv...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2011.12.013

    authors: Lee YJ,Chang JH,Choi HN,Jung JY,Kim YS,Chung WK,Park YH,Lee HH

    更新日期:2012-01-01 00:00:00

  • Natural History of Serum Calcium and Parathyroid Hormone Following Renal Transplantation.

    abstract:BACKGROUND:Hyperparathyroidism is common in end-stage renal disease. It often persists following renal transplantation (RTx) and remains elusive to manage due to the lack of evidence base. We therefore present observational data describing the natural history and management of hypercalcemia and hyperparathyroidism foll...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2016.09.050

    authors: Al-Moasseb Z,Aitken E

    更新日期:2016-12-01 00:00:00

  • Postexposure prophylaxis of H1N1 with oseltamivir in a newly transplanted kidney recipient receiving intense immunosuppressive therapy.

    abstract::Solid organ transplant recipients undergoing immunosuppressive therapy are considered to be at high risk for serious infectious complications. Recently in the United States, a pandemic of H1N1 flu infection has been reported with serious complications. We describe H1N1 infection in a living kidney donor and the 42-yea...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2009.09.052

    authors: Marfo K,Chapochnick-Friedmann J,Akalin E,Lu A

    更新日期:2009-12-01 00:00:00

  • Reliability of frozen section in the assessment of allograft steatosis in liver transplantation.

    abstract:BACKGROUND:Because liver allograft steatosis is an important risk factor of graft dysfunction after liver transplantation, it must be taken into consideration during graft acceptance. The aim of this study was to evaluate the reliability of frozen section in the assessment of liver steatosis before transplantation. ME...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2014.09.102

    authors: Hołówko W,Mazurkiewicz M,Grąt M,Koperski L,Lewandowski Z,Smoter P,Ziarkiewicz-Wróblewska B,Górnicka B,Zborowska H,Krawczyk M

    更新日期:2014-10-01 00:00:00

  • Kaposi sarcoma in solid organ transplant recipients: a single center report.

    abstract:BACKGROUND:Human herpes virus (HHV8) is associated with Castleman's disease, primary effusion lymphoma, and the Kaposi's sarcoma (KS). PATIENTS AND METHODS:Among 3815 solid organ transplants performed at our center between 1977 and 2003, five patients (0.1%) were identified with KS. RESULTS:There were one cardiac, on...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2005.03.144

    authors: Boeckle E,Boesmueller C,Wiesmayr S,Mark W,Rieger M,Tabarelli D,Graziadei I,Hoefer D,Antretter H,Stelzmueller I,Krugmann J,Zangerle R,Huemer H,Poelzl G,Margreiter R,Bonatti H

    更新日期:2005-05-01 00:00:00

  • Liver-Wrapping, Nitric Oxide-Releasing Nanofiber Downregulates Cleaved Caspase-3 and Bax Expression on Rat Hepatic Ischemia-Reperfusion Injury.

    abstract:BACKGROUND:Hepatic ischemia-reperfusion injury (IRI) is an important determinant of the outcome of hepatic surgery, including re-section and transplantation. Previous studies have shown that nitric oxide (NO) has a protective effect against IRI. Therefore, many studies have examined methods for supplying NO. In this st...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2017.03.054

    authors: Ko HM,Joo SH,Jo JH,Park WS,Jung WY,Shin JH,Ahn HJ

    更新日期:2017-06-01 00:00:00

  • Prognostic value of model for end-stage liver disease scores in patients with fulminant hepatic failure.

    abstract:BACKGROUND:This study was undertaken to investigate risk factors of mortality in patients with fulminant hepatic failure (FHF). METHODS:Fifty-three patients with FHF treated from January 2006 to April 2011 were allocated to a spontaneous survival group (group 1), a death without liver transplantation (LT) group (group...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2013.08.036

    authors: Lee HS,Choi GH,Joo DJ,Kim MS,Kim SI,Han KH,Ahn SH,Kim DY,Park JY,Choi JS

    更新日期:2013-10-01 00:00:00

  • Contrast-enhanced ultrasonography in the early period after kidney transplantation predicts long-term allograft function.

    abstract:INTRODUCTION:Real-time contrast-enhanced sonography (CES) can assess microvascular tissue perfusion using gas-filled microbubbles. The purpose of the study was to evaluate the feasibility of early CES in predicting long-term kidney allograft function in comparison to color Doppler ultrasonography (CDUS). METHODS:We pr...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2014.04.013

    authors: Schwenger V,Hankel V,Seckinger J,Macher-Göppinger S,Morath C,Zeisbrich M,Zeier M,Kihm LP

    更新日期:2014-12-01 00:00:00

  • Transplant of Tissue-Engineered Artificial Autologous Human Skin in Andalusia: An Example of Coordination and Institutional Collaboration.

    abstract::A new model of tissue-engineered artificial autologous human skin developed in Andalusia is currently being transplanted into patients suffering from large burns within the Andalusian Public Healthcare System. This product is considered an advanced therapy medicinal product (ATMP) in Europe, and its clinical use impli...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2019.08.014

    authors: Egea-Guerrero JJ,Carmona G,Correa E,Mata R,Arias-Santiago S,Alaminos M,Gacto P,Cuende N

    更新日期:2019-11-01 00:00:00

  • Thrombotic Ringed Polytetrafluoroethylene Graft With Infection After Living-Donor Liver Transplantation.

    abstract:BACKGROUND:The safety of the living donor in living-donor liver transplantation (LDLT) is always the first priority, meanwhile, the graft-to-recipient weight ratio (GRWR) and the anatomy of the liver allograft must also not be compromised in order to warrant tranplatation success. When it comes to the allograft of the ...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2018.04.050

    authors: Chung MH,Chuang CC,Liaw LF,Chen CY,Chen IM,Hsu CP,Lin NC,Loong CC

    更新日期:2018-11-01 00:00:00

  • Significance of Screening Tests and the Incidence of New Delhi Metallo-beta-lactamase-Producing Gram-negative Bacilli in the Surgery and Transplantation Wards of a Warsaw Medical Center During the Period From April 2014 to May 2017.

    abstract:BACKGROUND:The first New Delhi metallo-beta-lactamase (NDM)-producing bacteria were isolated in 2008 in the world, and in 2011 in Poland. Due to the high clonal diversity (17 types) of their blaNDM gene, encoded on (Tn125-like) mobile genetic elements, these strains usually exhibit resistance to nearly all available an...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2018.04.002

    authors: Szymanek-Majchrzak K,Mlynarczyk A,Kuthan R,Sawicka-Grzelak A,Majchrzak K,Kawecki D,Kosieradzki M,Durlik M,Deborska-Materkowska D,Paczek L,Mlynarczyk G

    更新日期:2018-09-01 00:00:00

  • Yearly Trends of Chronic Kidney Disease III Progressions in Living Kidney Donors.

    abstract:PURPOSE:We aim to see the rate of progression to chronic kidney disease stage III after living donor nephrectomy in a single institution annually. METHODS:Between May 2006 and July 2017, a total of 753 living kidney donors who were followed up more than 6 months were enrolled in the study. We divided normal function v...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2019.03.058

    authors: Lee HH,Na JC,Yoon YE,Lee HS,Huh KH,Kim YS,Han WK

    更新日期:2019-10-01 00:00:00

  • Experience with single-dose daclizumab in the prevention of acute rejection in heart transplantation.

    abstract:INTRODUCTION:Daclizumab is a monoclonal antibody that binds to the interleukin-2 receptor. It has been used as induction therapy in heart transplantation with two to five repeated administrations over several weeks. The objective of our study was to estimate the efficacy and safety of induction therapy with only one do...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2005.10.086

    authors: Cuppoletti A,Perez-Villa F,Vallejos I,Roig E

    更新日期:2005-11-01 00:00:00

  • Attitude of Scottish residents living in southeastern Spain toward organ donation.

    abstract:BACKGROUND:Southeastern Spain is a habitual area of residence for the native population of Scotland. OBJECTIVE:To assess the attitude toward donation in the immigrant population in our regional community who were born in Scotland and to analyze the variables that influence this attitude. MATERIALS AND METHODS:A rando...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2008.08.099

    authors: Ríos A,Cascales P,Martínez L,Ramírez P,Sánchez J,Jarvis N,Parrilla P

    更新日期:2008-11-01 00:00:00

  • Biliary tract complications after orthotopic liver transplantation: still the "Achilles heel"?

    abstract::Postoperative biliary tract complications after liver transplantation (LT) still lead to early and late morbidity and mortality. Modern interventional endoscopic techniques can replace surgical repair as the first line of treatment. Nevertheless surgical intervention plays an important role in specific situations. We ...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2010.09.045

    authors: Perrakis A,Förtsch T,Schellerer V,Hohenberger W,Müller V

    更新日期:2010-12-01 00:00:00

  • Level of Education and Knowledge of Skin Cancer Risk Factors in Patients Undergoing Maintenance Hemodialysis.

    abstract:INTRODUCTION:An increased risk of skin cancer is particularly important in patients undergoing maintenance hemodialysis (HD), who are potential transplant recipients. In transplant recipients who are exposed to immunosuppressive therapy, neoplastic skin disease my take a more aggressive course. Increased exposure to ph...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2018.02.098

    authors: Ankudowicz A,Król E,Dębska-Ślizień A,Czernych R

    更新日期:2018-01-01 00:00:00

  • Long-term Results of Living Donors in Simultaneous Kidney and Liver Transplantations.

    abstract:INTRODUCTION:Because of the shortage of organs available for transplantation, living related sequential transplantation with the use of liver and a kidney from the same donor has emerged as a reasonable therapeutic alternative. However, there is insufficient literature about the complications that living donors experie...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2017.01.020

    authors: Unek T,Egeli T,Özbilgin M,Çelik A,Atilla K,Ağalar C,Arslan NÇ,Karademir S,Bora S,Gülay H,Derici ZS,Astarcıoğlu I

    更新日期:2017-04-01 00:00:00

  • São Paulo lung transplantation waiting list: patient characteristics and predictors of death.

    abstract:INTRODUCTION:Nowadays, lung transplantation (LTx) allocation in Brazil is based mainly on waiting time. There is a need to evaluate the equity of the current lung allocation system. OBJECTIVES:We sought to (1) determine the characteristics of registered patients on the waiting list and (2) identify predictors of death...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2009.01.048

    authors: Costa da Silva F Jr,Afonso JE Jr,Pêgo-Fernandes PM,Caramori ML,Jatene FB

    更新日期:2009-04-01 00:00:00

  • Severe cardiac allograft dysfunction without endomyocardial biopsy signs of cellular rejection: incidence and management.

    abstract::Acute dysfunction of cardiac allograft without evidence of cellular rejection is a potentially fatal complication of heart transplantation that suggests a humoral origin. In clinical practice, humoral rejection (HR) is suspected when there is evidence of severe allograft dysfunction but endomyocardial biopsy (EMB) sho...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2004.03.033

    authors: Veiga Barreiro A,Crespo Leiro M,Doménech García N,Paniagua MJ,Vázquez Martul E,González Cuesta M,Ramírez C,Juffé Stein A,Castro Beiras A

    更新日期:2004-04-01 00:00:00

  • Exercise Training for Liver Transplant Candidates.

    abstract:BACKGROUND AND AIMS:Frailty is associated with increased morbidity and mortality, and this is tightly linked to liver decompensation and increased complication rates among liver transplant (LT) candidates. The aim of the study was to evaluate the efficacy of a structured in- and outpatient exercise training program for...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2019.08.045

    authors: Al-Judaibi B,Alqalami I,Sey M,Qumosani K,Howes N,Sinclair L,Chandok N,Eddin AH,Hernandez-Alejandro R,Marotta P,Teriaky A

    更新日期:2019-12-01 00:00:00