Project description:Gene expression data from wild-type and Bcl6-/- naive CD4 T cells In order to find genes regulated by Bcl6 in follicular helper T cells Naïve CD4 T cells were sorted from wild-type (WT) and T cell-specific conditional Bcl6-/- (KO) mice-- 8 samples, 4 WT and 4 KO
Project description:Gene expression data from wild-type and Bcl6-/- naive CD4 T cells In order to find genes regulated by Bcl6 in follicular helper T cells Naïve CD4 T cells were sorted from wild-type (WT) and T cell-specific conditional Bcl6-/- (KO) mice-- 8 samples, 4 WT and 4 KO
Project description:Epigenetic changes are crucial for the generation of immunological memory1-4. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing immune memory. Yet the transcription factors that regulate these processes are poorly defined, as are the chromatin modifying complexes they recruit and the chromatin modifications they control. Using pathogen infection models and three different mouse models, including a new conditional allele, we find that the widely expressed transcription factor Oct15, and its cofactor OCA-B6,7, are selectively required the in vivo generation of functional CD4 memory. In vitro, both proteins are also required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4 T cells, and to generate robust Il2 expression upon restimulation. OCA-B is also required for the robust re-expression of other known targets including Il17a, and Ifng. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a8 to targets such as Il2 and Ifng. The findings pinpoint Oct1 and OCA-B as unanticipated mediators of CD4 T cell memory. Examination of 4 different conditions in 2 genotypes
Project description:Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing immune memory. Yet the transcription factors that regulate these processes are poorly defined, as are the target genes they control and they chromatin-modifying complexes they recruit. Using model pathogens and three different mouse models, we find that the widely expressed transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of functional CD4 memory. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4 T cells, and to generate robust Il2 expression upon restimulation. Gene expression profiling indicates that OCA-B is also required for the robust re-expression of multiple other targets including Ifng and Il17a. ChIPseq identify multiple differentially expressed direct targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2 and Ifng. The findings pinpoint Oct1 and OCA-B as unanticipated mediators of CD4 T cell memory. Examination of transcription factor occupancy in CD4 T cells upon rest and restimulation.
Project description:Naïve T cells respond to antigen stimulation by exiting from quiescence into clonal expansion and functional differentiation, but the control mechanism is elusive. Here we describe that Raptor/mTORC1-dependent metabolic reprogramming is a central determinant of this transitional process. Loss of Raptor abrogates T cell priming and Th2 cell differentiation, although Raptor function is less important for continuous proliferation of actively cycling cells. mTORC1 coordinates multiple metabolic programs in T cells including glycolysis, lipid synthesis and oxidative phosphorylation to mediate antigen-triggered exit from quiescence. mTORC1 further links glucose metabolism to the initiation of Th2 differentiation by orchestrating cytokine receptor expression and cytokine responsiveness. Activation of Raptor/mTORC1 integrates T cell receptor (TCR) and CD28 co-stimulatory signals in antigen-stimulated T cells. Our studies identify a Raptor/mTORC1-dependent pathway linking signal-dependent metabolic reprogramming to quiescence exit, and this in turn coordinates lymphocyte activation and fate decisions in adaptive immunity. We used microarrays to explore the gene expression profiles differentially expressed in CD4+ T-cells from wild-type (WT) and CD4(cre) x Raptor(fl/fl) mice before and after stimulation with anti CD3/CD28 antibodies.
Project description:We aim to find the gene-specific effects of Rnmt KO in mouse CD4 T cells. TMT proteomics datasets were generated to find out which proteins are dependent on RNMT for their expression.
Project description:gene expression data from wild-type and Bcl6-/- regulatory T cells in order to find genes regulated by Bcl6 in Treg cells FoxP3+ Tregs were sorted from wild-type (WT) and Bcl6-/- (KO) mice-- 8 samples, 2 from each type of Treg, 2 WT and 2 KO
Project description:We observed significant growth inhibition of melanoma tumor in ROR?-/- mice, suggesting an important role for the T helper 17 cell (TH17) pathway in tumor immunity. Though RORgamma t (ROR?t) plays a critical role in the development of IL-17-secreting Th17 cells, the role of other genes remained an open question. To explore the expression of unknown genes with anti-tumor properties, gene expression analysis was performed. Sorted naïve TH cells (CD4+CD25-CD62Lhigh) from RORc+/+ and RORc-/-mice were differentiated under TH17 polarizing conditions. After 4 days, cells were harvested, RNA was isolated and gene expression analysis was performed.
Project description:We hypothesize that nuclear factors co-occupying the genetic elements with regulatory T (Treg) cell lineage–specifying factor Foxp3 play critical roles in transcriptional regulation of Treg immune suppression function, thus, offering a unique approach to investigate the factors and their mechanisms controlling Treg-mediated immune tolerance involved in self-tolerance and antitumor immunity. We seek to identify the proteins occupying Foxp3 targets in the resting state or after cells receiving stimulation. To this end, we projected the spatial information (PSI) of Foxp3, Histone H3, or Stat5 onto their adjacent proteins with peroxidase–catalyzed biotin-phenoxyl radicals and identify these biotinylated proteins with tandem mass tag (TMT)–based quantitative mass spectrometry (MS).