Human Double-Negative Regulatory T-Cells Induce a Metabolic and Functional Switch in Effector T-Cells by Suppressing mTOR Activity

Human Double-Negative Regulatory T-Cells Induce a Metabolic and Functional Switch in Effector T-Cells by Suppressing mTOR Activity Tabea Haug1, Michael Aigner1, Moritz M. Peuser1, Carolin D. Strobl1, Kai Hildner2, Dimitrios Mougiakakos1, Heiko Bruns1, Andreas Mackensen1 and Simon Völkl1* 1Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, University of Erlangen-Nuremberg, Erlangen, Germany 2Department of Internal Medicine 1, University Hospital Erlangen, University of Erlangen-Nuremberg, Erlangen, Germany The recently discovered population of TCRαβ+ CD4–/CD8– (double-negative, DN) T-cells are highly potent suppressor cells in mice and humans. In preclinical transplantation models, adoptive transfer of DN T-cells specifically inhibits alloreactive T-cells and prevents transplant rejection or graft-vs.-host disease (GvHD). Interestingly, clinical studies in patients who underwent allogeneic stem cell transplantation reveal an inverse correlation between the frequency of circulating DN T-cells and the severity of GvHD, suggesting a therapeutic potential of human DN T-cells. However, their exact mode of action has not been elucidated yet. Investigating the impact of DN T-cells on conventional T-cells, we found that human DN T-cells selectively inhibit mTOR signaling in CD4 T-cells. Given that mTOR is a critical regulator of cellular metabolism, we further determined the impact of DN T-cells on the metabo...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Publication date: Available online 22 February 2020Source: Journal of Pharmaceutical AnalysisAuthor(s): Max Sauter, Philipp Uhl, Jürgen Burhenne, Walter E. HaefeliAbstractExenatide is the first approved glucagon-like peptide 1 receptor agonist subcutaneously or intramuscularly injected for the treatment of type 2 diabetes mellitus. Typical therapeutic plasma concentrations are in the low pg/mL range therefore requiring ultra-sensitive quantification. To enable the accurate evaluation of pharmacokinetic studies, we established a UPLC-MS/MS assay with a lower limit of quantification (LLOQ) of 5 pg/mL (1.2 pM) using 20...
Source: Journal of Pharmaceutical Analysis - Category: Drugs & Pharmacology Source Type: research
Conclusion: Taken together, these results suggest that SXD maybe alleviate EMT in DN via the inhibition of the TGF-β1/Smad/RUNX3 signaling pathway under hyperglycemic conditions.Graphical abstract
Source: Phytomedicine - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 21 February 2020Source: Stem Cell ResearchAuthor(s): Yalan Zhou, Chengcheng Ding, Shutao Xia, Yutong Jing, Shengru Mao, Jian Liu, Juan Chen, Hon fai Chan, Shibo Tang, Jiansu ChenAbstractCrumbs homologue 1 (CRB1) mutations have been found in retinitis pigmentosa (RP) patients lead to severe retinal dystrophies. The human induced pluripotent stem (iPS) cell line CSUASOi003-A derived from peripheral blood mononuclear cells (PBMCs) of a patient carrying two heterozygous mutations (2249G>A p.G750D and c.2809G>A p.A937T) in CRB1 gene was generated by non-integrative reprogramming technolo...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
In this study, olfactory ensheathing cells (OECs) were cultured, chitosan (CS) was prepared, and the compatibility of CS and OECs was detected by MTT method. Animal model of chronic constrictive sciatic nerve injury (CCI) was made, OECs and OECs+CS were transplanted to the region surrounding the chronic sciatic nerve injury, and the difference between the two groups in the treatment of NPP was compared. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured by using behavioral method. In situ hybridization and Western-blotting were used to detect the expression of P2X4R mRNA and protei...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
Authors: Di Lullo L, Bellasi A, Guastamacchia E, Triggiani V, Ronco C, Lavalle C, Di Iorio BR, Russo D, Cianciolo G, La Manna G, Settembrini S Abstract Diabetes mellitus, with its complications, is one of the major health problems in economically developed countries and its prevalence is constantly increasing. Kidneys and heart involvement represent main comorbidities in diabetic patients often leading to organ's failure. The treatments available until a few years ago are often associated with hypoglycemia, weight gain, gastro-intestinal disorders and other side effects together with serious averse effects on renal...
Source: Minerva Cardioangiologica - Category: Cardiology Tags: Minerva Cardioangiol Source Type: research
Authors: De Vecchis R, Paccone A, Di Maio M Abstract BACKGROUND: The MacNew questionnaire in its original version is a diagnostic tool which consists of a number of questions answered on a seven-point scale. Among the multiple possible choices, each marked by a box, the examined patient will have to tick only one. In fact, more than one answer for each proposed question is not allowed, for the formulation of the final score. Global and subscale( physical, social and emotional subscales) scores are computed by dividing the sum of the scores achieved for each individual item by the number of items listed in the quest...
Source: Minerva Cardioangiologica - Category: Cardiology Tags: Minerva Cardioangiol Source Type: research
Authors: Cao M, Zhou M, Zhang J Abstract Patients with metastatic colorectal cancer (mCRC) beyond second line treatment have a poor prognosis. Regorafenib, TAS-102, fruquintinib, panitumumab and cetuximab are recommended single-agent chemotherapy regimens for patients exhibiting disease progression, this meta-analysis aimed to evaluate the efficacy and safety of these regimens in randomized controlled trials (RCTs). Eight RCTs with 3,832 cancer patients were included. Results showed that there was no significant difference in OS and PFS among the four drugs when comparing all patients or patients who have the KRAS ...
Source: Journal of Chemotherapy - Category: Cancer & Oncology Tags: J Chemother Source Type: research
CONCLUSION: The best of our knowledge it is the third description of brachial plexus schwannoma associated with breast cancer and the first with a synchronous association. The knowledge of this pathology and its potential to alter treatment justify the reporting of the present case. PMID: 32083563 [PubMed - as supplied by publisher]
Source: Breast Disease - Category: Cancer & Oncology Tags: Breast Dis Source Type: research
In this study, dosimeters were used to measure the testicular dose with and without testicular shielding to verify the effect of shielding. Anthropomorphic phantoms representing a human were used to estimate the doses absorbed in testicular and whole-body studies. The anthropomorphic phantom was irradiated according to the treatment protocol for colorectal cancer. Measurements were made using optically-stimulated luminescent dosimeters (OSLDs), composed of carbon-doped aluminum oxide, with characteristics suitable for radiotherapy dosimetry studies. A set of OSLDs was placed on a testicular phantom, attached to the lower e...
Source: Radiation Physics and Chemistry - Category: Physics Source Type: research
Publication date: 15 May 2020Source: Journal of Molecular Structure, Volume 1208Author(s): M.S. Ganesan, K. Kanmani Raja, K. Narasimhan, S. Murugesan, Banoth Karan KumarAbstractα-amylase enzyme hydrolyses carbohydrate into glucose is known to be an important molecular target for type 2 Diabetes mellitus. In the course of developing α-amylase enzyme inhibitors, we designed, synthesized seventeen novel quinoline bearing proline analogs, subsequently physico-chemical properties of designed analogs were also in silico predicted for their drug likeness evaluation. Synthesized compounds were characterized by spectral...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research
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