Thymic-derived regulatory T cell (tTreg) clinical trials show therapeutic promise in the prevention of acute graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation patients. However, strategies are needed to improve tTreg proliferative ability and survival as a means to improve tTreg therapy and reduce the requirement for producing large numbers of Treg cells for adoptive tTreg transfer. Autophagy is a self-degradative process for cytosolic components, which is involved in cells death, differentiation, lymphocyte homeostasis, and tTreg function. Studies have shown that mice with tTreg cells that have a disrupted autophagy process have defective tTreg cell generation and function, resulting in autoimmune disease and failed GVHD prevention by adoptively transferred tTreg cells. We found the attenuated autophagy status during ex vivo expansion, which leads us to determine whether tTreg cell survival could be augmented by miR-142-3p, the miRNA which is highly expressed in tTreg cells and potentially targets autophagy-related protein (ATG)-1, ATG16L1. We demonstrate that miR-142-3p downregulates ATG16L1 mRNA and production of ATG16L1, that has been linked to autoimmune diseases. Conversely, miR-142-3p knock-down improved tTreg cell expansion, survival and function in vitro and vivo. In aggregate, these studies provide a new approach that uses miR-142-3p knockdown to increase tTreg cell efficacy by increasing ATG16L1 mRNA and protein and the autophagy process.
Pubmed ID: 29459719 RIS Download
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Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsDatabase of microRNA target predictions and expression profiles. Target predictions are based on a development of the miRanda algorithm which incorporates current biological knowledge on target rules and on the use of an up-to-date compendium of mammalian microRNAs. MicroRNA expression profiles are derived from a comprehensive sequencing project of a large set of mammalian tissues and cell lines of normal and disease origin. This website enables users to explore: * The set of genes that are potentially regulated by a particular microRNA. * The implied cooperativity of multiple microRNAs on a particular mRNA. * MicroRNA expression profiles in various mammalian tissues. The web resource provides users with functional information about the growing number of microRNAs and their interaction with target genes in many species and facilitates novel discoveries in microRNA gene regulation. The microRNA Target Detection Software, miRanda, is an algorithm for finding genomic targets for microRNAs. This algorithm has been written in C and is available as an open-source method under the GPL.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
View all literature mentionsWeb tool to predict biological targets of miRNAs by searching for presence of conserved 8mer, 7mer and 6mer sites that match seed region of each miRNA. Nonconserved sites are also predicted and sites with mismatches in seed region that are compensated by conserved 3' pairing. Used to search for predicted microRNA targets in mammals.
View all literature mentionsAn online database for miRNA target prediction and functional annotations.
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
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