Project description:Activation of NFkB pathway by CARD11 Cy3-labelled untreated sample and Cy5-labelled treated sample were hybridized to a Lymphochip microarray.
Project description:In order to investigate the molecular mechanism of CARD11 in immune cell system, we applied the RNA-seq analysis using RNA isolated from WT and CARD11 mutant (E134G and K215M) mouse spleen B cells. By comparing the transcriptome files, we found some different expressed gene involved in due to the CARD11 point mutation and in vitro RT-PCR had confirmed this result.
Project description:CARD11 LOF mutant patients develop severe atopic phenotpes and increased T-helper 2 (Th2) cytokine production, in addition to other immunopathology. CARD11 LOF impairs lymphocyte receptor–mediated glutamine uptake—thereby reducing signaling in mTORC1. Herein, we investigate whether exogenous glutamine treatment would alleviate Th2 phenotypes of CARD11 LOF mutant T cells.
Project description:Antigen receptor signaling pathways that control lymphocyte activation depend upon signaling hubs and negative regulatory proteins to fine-tune signaling output to ensure host defense and avoid potentially pathogenic hyperresponses. CARD11 is a critical signaling scaffold that translates T Cell Receptor triggering into the activation of branching NF-kB, JNK, mTOR and Akt pathways. Here we identify QRICH1 as a regulator of CARD11 signaling that mediates a previously undiscovered intracellular checkpoint for CD8+ T cell activation. QRICH1 inducibly associates with CARD11 following TCR engagement and negatively regulates CARD11 signaling to the IKK complex and NF-kB. QRICH1 binding to CARD11 occurs after TCR-induced CARD11 opening and is controlled by an autoregulatory intramolecular interaction between QRICH1 protein domains of previously uncharacterized function. Using mice deficient in QRICH1 in the T cell lineage, we show that QRICH1 controls the antigen-induced activation, proliferation, and effector status of CD8+ T cells by regulating numerous gene targets critical for CD8+ T cell function. Our results define a previously unappreciated component of antigen receptor signaling circuitry that fine-tunes effector output in response to antigen recognition.
Project description:We describe the use of saturation genome editing to measure the effects of CARD11 variants on protein function, splicing and lymphoma cell survival. We find the results to predict the clinical effects of the variants.
Project description:E.coli K-12 W3110 was grown in LB medium and harvested at each time point. And time series microarray experiments were performed based on reference desgin. In reference design, the control sample is collected at one representative time point. Combining with data from sequential design, more acculate and reliable expression series could be collected. Keywords: Reference design
Project description:E.coli K-12 W3110 was grown in LB medium and harvested at each time point. And time-series microarray experiments were performed based on Sequential Design. In Sequential Design, the control sample is set to closest previous time point so that adjacent time points are compared directly. Combining with data from reference design, more accurate and reliable expression series could be collected. Keywords: timecourse