Project description:cAMP inhibits TCR signaling, T cell proliferation, cytokine production and T cell function. We used microarrays to detail the global programme of gene expression in TCR-activated WT or IFN-gR1-deficient CD4+ T cells by db-cAMP. CD4+ T cells were purified from spleens of WT or IFN-gR1-deficient mice by autoMACS, and activated with anti-CD3 plus anti-CD28 for 15 h. db-cAMP or vehicle control (med) was added into cultures for the last 3 h.
Project description:cAMP inhibits TCR signaling, T cell proliferation, cytokine production and T cell function. We used microarrays to detail the global programme of gene expression in TCR-activated WT or IFN-gR1-deficient CD4+ T cells by db-cAMP.
Project description:<p>Interferon (IFN)-stimulated gene 15 (ISG15) regulates diverse cellular processes, including antiviral immunity, through its conjugation to target proteins (ISGylation). Increasing evidence suggests that ISGylation can also reshape cellular metabolism; however, how viruses counteract ISGylation-mediated metabolic rewiring remains poorly understood. This analysis investigated the impact of the deISGylation activity of the SARS-CoV-2 papain-like protease, which is part of the Nsp3 protein, on type I IFN-driven modulation of cellular glucose metabolism. A549 cells expressing empty vector, wild-type (WT) Nsp3-4 from SARS-CoV-2, or a mutant Nsp3-4 protein that is deficient in PLpro deISGylation activity, were treated with IFNα (or mock-treated) and then subjected to 13C-glucose tracing analysis. Following isotope labeling, intracellular metabolites were extracted and analyzed by LC-MS to assess 13C incorporation into intermediates of glycolysis and the pentose phosphate pathway (PPP). Comparative analysis of the results revealed distinct labeling patterns in glycolytic and PPP metabolites under IFN-stimulated conditions, supporting a role for PLpro deISGylation activity in modulating cellular glucose metabolism. These data provide insight into how SARS-CoV-2 Nsp3 counteracts IFN-induced metabolic rewiring through its deISGylation activity.</p>
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
