Project description:We report that Stat6-driven gene transcription regulates the transition from Tfh21 to Tfh4 cells, suppressing IL-21 production and promoting IL-4 secretion. We identified a cis-enhancer in the second intron of Il21 as a regulator of Tfh cell cytokine transition, via an effect of Stat6 on chromatin accessibility with repression of Il21 transcription. We conclude that Stat6 is necessary for coordinated regulation of IL-21 and IL-4 production by Tfh cells, leading to appropriate maturation of the germinal center B cell response.
Project description:We report that Stat6-driven gene transcription regulates the transition from Tfh21 to Tfh4 cells, suppressing IL-21 production and promoting IL-4 secretion. We identified a cis-enhancer in the second intron of Il21 as a regulator of Tfh cell cytokine transition, via an effect of Stat6 on chromatin accessibility with repression of Il21 transcription. Chromatin accessibitiy of this second intron region was not affected in the naive CD4+ T cell population
Project description:Purpose: To examine the expression profile of WT and Stat6 KO intestinal stem cells. Methods: We isolated Lgr5+ ISCs from the intestine tissue, and generated Stat6 KO ISCs through CRISPR/Cas9 approach. Results: Many genes are changed upon Stat6 KO cells. We pay special attention on Wnt/β-catenin signaling that is the most critical pathway in ISCs, and discovered Stat6 drove the expression of Wnt target genes. Conclusions: Stat6 crosstalks with Wnt signaling to drive ISC self-renewal.
Project description:We report that Stat6-driven gene transcription regulates the transition from Tfh21 to Tfh4 cells, suppressing IL-21 production and promoting IL-4 secretion. We identified a cis-enhancer in the second intron of Il21 as a regulator of Tfh cell cytokine transition, via an effect of Stat6 on chromatin accessibility with repression of Il21 transcription. We conclude that Stat6 is necessary for coordinated regulation of IL-21 and IL-4 production by Tfh cells, leading to appropriate maturation of the germinal center B cell response.
Project description:Interventions: experimental group :PD-1 Knockout Engineered T Cells
Primary outcome(s): Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and tolerability of dose of PD-1 Knockout T cells using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients
Study Design: historical control
Project description:IL-4/STAT6-regulated transcriptome and proteome were compared in primary B cells isolated from wild-type and STAT6-deficient mice. B cells were purified from the spleen and stimulated in vitro with anti-CD40 and LPS or anti-IgM-F(ab)2 in the presence or absence of IL-4. Transcriptome analysis was performed with oligonucleotide microarrays. Global relative quantification of proteins was achieved by gel-enhanced label-free liquid chromatography/mass spectrometry (LC/MS). Hierarchical clustering and principal component analysis revealed that IL-4-induced changes of the transcriptome were almost completely dependent on STAT6. In contrast, the quantitative proteome analysis revealed that the expression of many IL-4-regulated proteins changes even in the absence of STAT6. The top 75 proteins with changes in abundance levels induced by IL-4 in a STAT6-dependent manner were also found to be regulated at the transcriptional level. Most of these proteins were not previously known to be regulated by STAT6 in B cells. We confirmed the MS-based quantitative proteome data by flow cytometric and Western blot analysis of selected proteins. This study provides a framework for further functional characterization of STAT6-regulated proteins in B cells that might be involved in germinal center formation and class switch recombination.