Regulatory T (Treg) cells are essential for maintaining immune homeostasis and tolerance, but the mechanisms regulating the stability and function of Treg cells have not been fully elucidated. Here we show SUMO-specific protease 3 (SENP3) is a pivotal regulator of Treg cells that functions by controlling the SUMOylation and nuclear localization of BACH2. Treg cell-specific deletion of Senp3 results in T cell activation, autoimmune symptoms and enhanced antitumor T cell responses. SENP3-mediated BACH2 deSUMOylation prevents the nuclear export of BACH2, thereby repressing the genes associated with CD4+ T effector cell differentiation and stabilizing Treg cell-specific gene signatures. Notably, SENP3 accumulation triggered by reactive oxygen species (ROS) is involved in Treg cell-mediated tumor immunosuppression. Our results not only establish the role of SENP3 in the maintenance of Treg cell stability and function via BACH2 deSUMOylation but also clarify the function of SENP3 in the regulation of ROS-induced immune tolerance.
Alzheimer's disease (AD) is an incurable neurodegenerative disease and many types of stem cells have been used in AD therapy with some favorable effects. In this study, we investigated the potential therapeutical effects of human dental pulp stem cells (hDPSCs) on AD cellular model which established by okadaic acid (OA)-induced damage to human neuroblastoma cell line, SH-SY5Y, in vitro for 24 h. After confirmed the AD cellular model, the cells were co-culture with hDPSCs by transwell co-culture system till 24 h for treatment. Then the cytomorphology of the hDPSCs-treated cells were found to restore gradually with re-elongation of retracted dendrites. Meanwhile, Cell Counting Kit-8 assay and Hoechst 33258 staining showed that hDPSCs caused significant increase in the viability and decrease in apoptosis of the model cells, respectively. Observation of DiI labeling also exhibited the prolongation dendrites in hDPSCs-treated cells which were obviously different from the retraction dendrites in AD model cells. Furthermore, specific staining of α-tubulin and F-actin demonstrated that the hDPSCs-treated cells had the morphology of restored neurons, with elongated dendrites, densely arranged microfilaments, and thickened microtubular fibrils. In addition, results from western blotting revealed that phosphorylation at Ser 396 of Tau protein was significantly suppressed by adding of hDPSCs. These results indicate that hDPSCs may promote regeneration of damaged neuron cells in vitro model of AD and may serve as a useful cell source for treatment of AD.
Metabolic programs are crucial for regulatory T (T reg) cell stability and function, but the underlying mechanisms that regulate T reg cell metabolism are elusive. Here, we report that lysosomal TRAF3IP3 acts as a pivotal regulator in the maintenance of T reg cell metabolic fitness. T reg-specific deletion of impairs T reg cell function, causing the development of inflammatory disorders and stronger antitumor T cell responses in mice. Excessive mechanistic target of rapamycin complex 1 (mTORC1)-mediated hyper-glycolytic metabolism is responsible for the instability of TRAF3IP3-deficient T reg cells. Mechanistically, TRAF3IP3 restricts mTORC1 signaling by recruiting the serine-threonine phosphatase catalytic subunit (PP2Ac) to the lysosome, thereby facilitating the interaction of PP2Ac with the mTORC1 component Raptor. Our results define TRAF3IP3 as a metabolic regulator in T reg cell stability and function and suggest a lysosome-specific mTORC1 signaling mechanism that regulates T reg cell metabolism.
Carcinomas are complex ecosystems composed of cancer, stromal and immune cells. Communication between these cells and their microenvironments induces cancer progression and causes therapy resistance. In order to improve the treatment of cancers, it is essential to quantify crosstalk between and within various cell types in a tumour microenvironment. Focusing on the coordinated expression patterns of ligands and cognate receptors, cell–cell communication can be inferred through ligand–receptor interactions (LRIs). In this manuscript, we carry out the following work: (i) introduce pipeline for ligand–receptor-mediated intercellular communication estimation from single-cell transcriptomics and list a few available LRI-related databases and visualization tools; (ii) demonstrate seven classical intercellular communication scoring strategies, highlight four types of representative intercellular communication inference methods, including network-based approaches, machine learning-based approaches, spatial information-based approaches and other approaches; (iii) summarize the evaluation and validation avenues for intercellular communication inference and analyze the advantages and limitations for the above four types of cell–cell communication methods; (iv) comment several major challenges while provide further research directions for intercellular communication analysis in the tumour microenvironments. We anticipate that this work helps to better understand intercellular crosstalk and to further develop powerful cell–cell communication estimation tools for tumor-targeted therapy.
This paper describes our submissions to task 8 in SemEval 2017, i.e., Determining rumour veracity and support for rumours. Given a rumoured tweet and a plethora of replied tweets, subtask A is to label whether these tweets are support, deny, query or comment, and subtask B aims to predict the veracity (i.e., true, false, and unverified) with a confidence (in range of 0-1) of the given rumoured tweet. For both subtasks, we adopted supervised machine learning methods incorporating rich features. Since the training data is imbalanced, we specifically designed a two-step classifier to address subtask A .
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.