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mtor immunology

Davood Rostamzadeh, Mehdi Yousefi, Mohammad Reza Haghshenas, Majid Ahmadi, Sanam Dolati, Zohreh Babaloo
The mammalian target of rapamycin (mTOR) is a member of the evolutionary phosphatidylinositol kinase-related kinases (PIKKs). mTOR plays a pivotal role in the regulation of diverse aspects of cellular physiology such as body metabolism, cell growth, protein synthesis, cell size, autophagy, and cell differentiation. Immunologically, mTOR has a fundamental part in controlling and shaping diverse functions of innate and adaptive immune cells, in particular, T-cell subsets differentiation, survival, and metabolic reprogramming to ultimately regulate the fate of diverse immune cell types...
February 2, 2019: Journal of Cellular Physiology
Chuanlin Ding, Xiaomin Sun, Caijun Wu, Xiaoling Hu, Huang-Ge Zhang, Jun Yan
The role of the mTOR signaling pathway in different myeloid cell subsets is poorly understood in the context of tumor development. In this study, myeloid cell-specific Raptor knockout (KO) mice were used to determine the roles of mechanistic target of rapamycin complex 1 (mTORC1) in regulating macrophage function from Lewis lung carcinoma (LLC) s.c. tumors and lung tumor metastasis. We found no difference in tumor growth between conditional Raptor KO and control mice in the s.c. tumor models, although depletion of mTORC1 decreased the immunosuppressive function of tumor-associated macrophages (TAM)...
January 21, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Yann-Alexandre Vano, Audrey Simonaggio, Constance Thibault, Stéphane Oudard
Clear cell kidney cancer is a tumour type whose development and progression is driven by the HIF/VEGF angiogenesis pathway. Anti-angiogenic (AA) agents, particularly anti-VEGFR tyrosine kinase (TKI) inhibitors, have profoundly modified the prognosis of patients in the metastatic setting (mRCC) since their registration in 2006. At the same time, mTOR inhibitors have also brought significant benefit to patients. More recently, treatments restoring adaptive anti-tumor immunity, anti-program death 1 (anti-PD-1) checkpoint inhibitors (ICP), have in turn revolutionized the management of patients with mRCC...
December 2018: Bulletin du Cancer
S Wei, S Xie, Z Yang, X Peng, L Gong, K Zhao, K Zeng, K Lai
OBJECTIVE: The aim of our study was to investigate the efficacy of adipose-derived stem cells (ADSC) transplantation in systemic lupus erythematosus (SLE) and to determine the mechanism of ADSC transplantation. METHODS: B6.MRL/lpr mice were administered ADSC intravenously every week from age 28 to 31 weeks, while the lupus control group and the normal control received phosphate buffered solution (PBS) on the same schedule. RESULTS: Compared with the lupus control group, the ADSC treatment group had a significant improvement of histologic abnormalities, serologic abnormalities, and immunologic function...
December 20, 2018: Lupus
Laurence Booth, Jane L Roberts, Cindy Sander, Alshad S Lalani, John M Kirkwood, John F Hancock, Andrew Poklepovic, Paul Dent
There is no efficacious standard of care therapy for uveal melanoma. Unlike cutaneous disease, uveal melanoma does not exhibit RAS mutations but instead contains mutations with ~90% penetrance in either Gαq or Gα11 . Previously we demonstrated that neratinib caused ERBB1/2/4 and RAS internalization into autolysosomes which resulted in their proteolytic degradation. In PDX isolates of uveal melanoma, neratinib caused the internalization and degradation of Gαq and Gα11 in parallel with ERBB1 breakdown. These effects were enhanced by the HDAC inhibitor entinostat...
December 20, 2018: Cancer Biology & Therapy
Laila Almeida Viana, Marina P Cristelli, Daniel Wagner Santos, Melissa G Tavares, Marcus Taver C Dantas, Claudia Rosso Felipe, Helio Tedesco Silva, Jose Medina Pestana
Tuberculosis (TB) mortality is high among kidney transplant (KT) recipients. Although local epidemiology is an important factor, diagnostic/therapeutic challenges and immunosuppressive therapy (ISS) may influence outcomes. We analyzed the cumulative incidence (CumI) of TB in KT recipients receiving a variety of ISS with long-term follow-up. Our retrospective single-center cohort study included all KT procedures performed between January 1, 1998, and August 31, 2014, with follow-up until August 31, 2014. Induction therapy was based on perceived immunological risk; maintenance ISS included prednisone and calcineurin inhibitor (CNI) plus azathioprine (AZA), and mycophenolic acid (MPA) or mechanistic target of rapamycin inhibitor (mTORi)...
December 17, 2018: American Journal of Transplantation
Ying Wang, Wenjie Wang, Luyao Liu, Jia Hou, Wenjing Ying, Xiaoying Hui, Qinhua Zhou, Danru Liu, Haili Yao, Jinqiao Sun, Xiaochuan Wang
PURPOSE: We aimed to report the clinical manifestations and immunological features of activated phosphatidylinositol 3-kinase δ syndrome 1 (APDS1) in a Chinese cohort. Moreover, we investigated the efficacy and safety of rapamycin therapy for Chinese patients with APDS1. METHODS: Fifteen Chinese patients with APDS1 from 14 unrelated families were enrolled in this study. These patients were diagnosed based on clinical features, immunological phenotype, and whole-exome sequencing...
November 29, 2018: Journal of Clinical Immunology
Qian-Hang Shao, Xiao-Ling Zhang, Ying Chen, Cheng-Gen Zhu, Jian-Gong Shi, Yu-He Yuan, Nai-Hong Chen
No abstract text is available yet for this article.
September 2018: Molecular Immunology
Stergios Boussios, Michele Moschetta, Afroditi Karathanasi, Alexandros K Tsiouris, Foivos S Kanellos, Konstantina Tatsi, Konstantinos H Katsanos, Dimitrios K Christodoulou
Malignant peritoneal mesothelioma (MPM) is a rare disease with a wide clinical spectrum. It arises from the peritoneal lining and commonly presents with diffuse, extensive spread throughout the abdomen and, more rarely, metastatic spread beyond the abdominal cavity. Computed tomography, magnetic resonance imaging and positron-emission tomography are important diagnostic tools used for the preoperative staging of MPM. The definitive diagnosis is based on histopathological analysis, mainly via immunohistochemistry...
November 2018: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
Yating Li, Longxian Lv, Jianzhong Ye, Daiqiong Fang, Ding Shi, Wenrui Wu, Qing Wang, Jingjing Wu, Liya Yang, Xiaoyuan Bian, Xianwan Jiang, Huiyong Jiang, Ren Yan, Conggao Peng, Lanjuan Li
Acute liver failure is a drastic, unpredictable clinical syndrome with high mortality. Various preventive and adjuvant therapies based on modulating the gut flora have been proposed for hepatic injury. We aimed to explore the preventive and therapeutic effects of Bifidobacterium adolescentis CGMCC15058 on rat liver failure, as well as the potential microecological and immunological mechanisms of those effects. B. adolescentis CGMCC15058 (3 × 109  CFU), isolated from healthy human stool, was gavaged to Sprague-Dawley rats for 14 days...
October 22, 2018: Applied Microbiology and Biotechnology
Fatema Z Chowdhury, Zhengyu Ouyang, Maria Buzon, Bruce D Walker, Mathias Lichterfeld, Xu G Yu
OBJECTIVE: Elite controllers, defined as persons maintaining undetectable levels of HIV-1 replication in the absence of antiretroviral therapy, represent living evidence that sustained, natural control of HIV-1 is possible, at least in relatively rare instances. Understanding the complex immunologic and virologic characteristics of these specific patients holds promise for inducing drug-free control of HIV-1 in broader populations of HIV-1 infected patients. DESIGN: We used an unbiased transcriptional profiling approach to characterize CD8 T cells, the strongest correlate of HIV-1 immune control identified thus far, in a large cohort of elite controllers (n = 51); highly active antiretrovial therapy (HAART)-treated patients (n = 32) and HIV-1 negative (n = 10) served as reference cohorts...
November 28, 2018: AIDS
Ying Luo, Yu Xia, Wenjing Wang, Zhichuan Li, Yan Jin, Yifeng Gong, Tingyan He, Qiu Li, Chengrong Li, Jun Yang
Activated phosphoinositide 3-kinase δ (PI3Kδ) syndrome is a newly defined and relatively common primary immunodeficiency, which is caused by heterozygous gain-of-function (GOF) mutations in PIK3CD or PIK3R1. Here, we report a novel de novo GOF mutation (c.1570 T > A, p.Y524N) in PIK3CD in a 6-year-old Chinese girl. The patient suffered recurrent sinopulmonary infection, bronchiectasis, lymphoproliferation, herpesvirus infection, and distinctive nodular lymphoid hyperplasia of mucosal surfaces. Immunological analysis revealed increased CD4+ T cell senescence and B cell immaturity...
August 20, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Tamara da Silva Vaccaro, Julia Medeiros Sorrentino, Sócrates Salvador, Tiago Veit, Diogo Onofre Souza, Roberto Farina de Almeida
Aims: Autism spectrum disorder (ASD) refers to a group of heterogeneous brain-based neurodevelopmental disorders with different levels of symptom severity. Given the challenges, the clinical diagnosis of ASD is based on information gained from interviews with patients' parents. The heterogeneous pathogenesis of this disorder appears to be driven by genetic and environmental interactions, which also plays a vital role in predisposing individuals to ASD with different commitment levels. In recent years, it has been proposed that epigenetic modifications directly contribute to the pathogenesis of several neurodevelopmental disorders, such as ASD...
August 15, 2018: Behavioral Sciences
S Mann, A Sipka, F A Leal Yepes, D V Nydam, T R Overton, J J Wakshlag
Transition dairy cows experience a nutrient deficit, particularly in the immediate postpartum period. At the same time, the inflammatory balance is altered and cows exhibit an immune response primed for inflammatory response rather than tolerance. The mechanistic link that might be underlying the immunological effects due to the lack in nutrients is not fully understood. Studies in other species demonstrate an orchestrating role of nutrient-sensing kinases in the determination of immune phenotypes and immune cell proliferation and differentiation...
July 25, 2018: Journal of Dairy Science
Jiacheng Zeng, Banghao Zhu, Meiling Su
Acetylshikonin (AS), a naphthoquinone constituent derived from Lithospermum erythrorhizon, has been revealed various pharmacological activities including anti-oxidative, anti-inflammatory and antifertility effects. Our previous study has illuminated the effects of AS on preventing obesity and hepatic steatosis in db/db mice. However, the effects of AS and the molecular mechanisms for curing non-alcoholic steatohepatitis (NASH) have not yet been studied. Autophagy has been considered as a lysosomal degradative pathway responsible for the removal of cellular lipid droplets through a process called lipophagy, which is recognized as a potential therapeutic approach for NASH...
September 10, 2018: Biochemical and Biophysical Research Communications
Xia Meng, Xinrong Sun, Yonghong Zhang, Hongyang Shi, Wenjing Deng, Yanqin Liu, Guizuo Wang, Ping Fang, Shuanying Yang
Peroxisome proliferator-activated receptor-γ (PPARγ) agonist pioglitazone (PGZ) exhibits potential protective effects in asthma. Recently, regulator of G protein 4 (RGS4) has been reported to be associated with immunological and inflammatory responses. However, no evidence has shown the influence of PPARγ on RGS4 expression in airway disorders. In this study, BALB/c mice received ovalbumin (OVA) sensitization followed by OVA intranasal challenge for 90 days to establish a chronic asthma mouse model. Accompanied with OVA challenge, the mice received administration of PPARγ agonist PGZ (10 mg/kg) intragastrically or RGS4 inhibitor CCG 63802 (0...
December 2018: Inflammation
Pio Conti, Alessandro Caraffa, Gianpaolo Ronconi, Spiros K Kritas, Filiberto Mastrangelo, Lucia Tettamanti, Ilias Frydas, Theoharis C Theoharides
OBJECTIVE: The aim of this study was to evaluate the role of mast cells (MCs) in allograft rejection, eventually inhibited by IL-37. Immune cells including MCs participate in allograft rejection by generating IL-1, IL-33, TNF and other cytokines. METHODS: We evaluated allograft rejection on the experience of our experimental data and using the relevant literature. RESULTS: MCs are involved in initiation and regulation of innate and adaptive immune responses-pathways...
September 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Imerio Angriman, Lucrezia Furian, Melania Scarpa, Matteo Fassan, Susan Morgan, Andrea Porzionato, Andromachi Kotsafti, Luca Saadeh, Cristina Silvestre, Raffaele De Caro, Amedeo Carraro, Umberto Tedeschi, Romeo Bardini, Paolo Rigotti, Massimo Rugge, Carlo Castoro, Ignazio Castagliuolo, Marco Scarpa
BACKGROUND: Ulcerative colitis patients and transplant recipients are at risk for colorectal cancer. Here, we show that immunosuppressive regimens for kidney transplants are associated with the progression of ulcerative colitis-related carcinogenesis. METHODS: We describe the case of a patient diagnosed with colorectal cancer in ulcerative colitis while on immunosuppressive therapy for a kidney transplant. The immunological microenvironment of the cancer and its mutational status were analyzed, and a mouse colon cancer model was created to replicate the unique clinical conditions...
June 19, 2018: Oncogenesis
Jessica Mandrioli, Roberto D'Amico, Elisabetta Zucchi, Annalisa Gessani, Nicola Fini, Antonio Fasano, Claudia Caponnetto, Adriano Chiò, Eleonora Dalla Bella, Christian Lunetta, Letizia Mazzini, Kalliopi Marinou, Gianni Sorarù, Sara de Biasi, Domenico Lo Tartaro, Marcello Pinti, Andrea Cossarizza
INTRODUCTION: Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions...
June 2018: Medicine (Baltimore)
Sophie Jung, Laura Gámez-Díaz, Michele Proietti, Bodo Grimbacher
Primary immunodeficiencies (PIDs) represent a group of mostly monogenic disorders caused by loss- or gain-of-function mutations in over 340 known genes that lead to abnormalities in the development and/or the function of the immune system. However, mutations in different genes can affect the same cell-signaling pathway and result in overlapping clinical phenotypes. In particular, mutations in the genes encoding for members of the phosphoinositide3-kinase (PI3K)/AKT/mTOR/S6 kinase (S6K) signaling cascade or for molecules interacting with this pathway have been associated with different PIDs that are often characterized by the coexistence of both immune deficiency and autoimmunity...
2018: Frontiers in Immunology
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