Project description:Extracellular adenosine triphosphate (eATP) is a signaling molecule that affects T cell function via the ionotropic P2X7 receptor. The study of effector/memory T cells isolated from mice with deletion of P2rx7, the gene encoding for P2X7, allowed understanding the impact of P2X7 activity on T cell function in the eATP-rich tumor microenvironment. To explore the the transcriptional impact of the lack of P2rx7 in CD4+ naïve and TEM cells, we performed genome-wide expression profiling of ex vivo purified CD4+ naïve and TEM cells from WT and P2rx7-/- mice
Project description:CD4+ T cells are key components of the immune response during lung infections and can mediate protection against tuberculosis (TB) or influenza. However, CD4+ T cells can also promote lung pathology during these infections, making it unclear how these cells control such discrepant effects. Using mouse models of hypervirulent TB and influenza, we observed that exaggerated accumulation of parenchymal CD4+ T cells promotes lung damage. Low numbers of lung CD4+ T cells, in contrast, are sufficient to protect against hypervirulent TB. In both situations, lung CD4+ T cell accumulation is mediated by CD4+ T cell-specific expression of the extracellular ATP (eATP) receptor P2RX7. P2RX7 upregulation in lung CD4+ T cells promotes expression of the chemokine receptor CXCR3 and favors in situ proliferation. Our findings suggest that direct sensing of lung eATP by CD4+ T cells is critical to induce tissue CD4+ T cell accumulation and pathology during lung infections.
Project description:H3K36me3 ChIP sequencing performed on circulating ex vivo isolated CD4+ Naive T cells under LINE1 RNA knock-down and control conditions
Project description:Compare ex vivo unstimulated CD4 T cells from SLE and HC female patients in an ethnically mixed cohort for transcriptional differences.
Project description:Duchenne muscular dystrophy (DMD) is a debilitating and typically fatal X-linked progressive neuromuscular disorder that results in progressive muscle degeneration aggravated by sterile inflammation. The P2RX7 purinoceptor is an extracellular ATP-gated ion channel expressed in immune cells, and has been targeted in treatment of infectious and inflammatory diseases. In particular, P2xr7 receptor abnormalities have been demonstrated in mdx dystrophic mice, a model for DMD lacking expression of the full length dystrophin transcript through a single point mutation in exon 23. Here, we looked at the differential effects in gene expression regulation in whole muscle in dystrophic mdx mice with or without ablation of the P2rx7 purinoceptor.
Project description:The development and propagation of an adaptive immune response to an invading pathogen is a highly orchestrated process that involves the precise regulation of cytokine expression. Naïve CD4+ T lymphocytes give rise to T helper (Th) cell subsets with functions that are tailored to their respective roles in host defense. MicroRNAs are important regulators of most cellular processes, including many responses in the immune system. To identify novel microRNAs that might be important in human T helper cell differentiation to different subsets we purified T cell subsets from peripheral blood and performed microRNA arratys at Exiqon. Naïve, Th1, Th2, Th17 and Tregs were FACS-sorted ex-vivo from peripheral blood of 6-11 donors. Due to the very low amount of starting material total RNA from at least 6 different donors was pooled and anlaysed on the arrays. All samples were analyzed against a common reference, which was made by pooling together a small amount of total CD4+ cells from all donors.