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IL-33, which is a crucial modulator of adaptive immune responses far beyond type 2 response, can enhance the function of several T cell subsets and maintain the immune homeostasis. However, the contribution of IL-33 to double negative T (DNT) cell remains unappreciated. Here, we demonstrated that the IL-33 receptor ST2 was expressed on DNT cells, and that IL-33 stimulation increased DNT cells proliferation and survival in vivo and in vitro. Transcriptome sequencing analysis also demonstrated that IL-33 enhanced the biological function of DNT cells, especially effects on proliferation and survival. IL-33 promoted DNT cells survival by regulating Bcl-2, Bcl-xl and Survivin expression. IL-33-TRAF4/6-NF-κB axis activation promoted the transmission of essential division and survival signals in DNT cells. However, IL-33 failed to enhance the expression of immunoregulatory molecules in DNT cells. DNT cells therapy combined with IL-33 inhibited T cells survival and further ameliorated ConA-induced liver injury, which mainly depended on the proliferative effect of IL-33 on DNT cells in vivo. Finally, we stimulated human DNT cells with IL-33, and similar results were observed. In conclusion, we revealed a cell intrinsic role of IL-33 in the regulation of DNT cells, thereby identifying a previously unappreciated pathway supporting the expansion of DNT cells in the immune environment.
Pubmed ID: 37019882
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Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsPrivately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsSoftware 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 mentionsAn Organization portal, Antibody supplier, Service resource,
View all literature mentionsAmerican chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.
View all literature mentionsIntegrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsPrivately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionslaboratory mouse with name B6D2F1 from MGI.
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