Dhx9 controls effector CD8 T cell differetiation program
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ABSTRACT:
PROVIDER: PRJNA678442 | ENA |
REPOSITORIES: ENA
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Project description:We provide differentially gene expression between wt and Dhx9-/- CD8 T cells from LCMV infected mice.
2020-11-15 | GSE161489 | GEO
Project description:Nuclear sensor molecules of innate cells recognize pathogenic DNA or RNA to activate innate immunity and defense against bacteria and virus infection. Although some sensors exhibit their preliminary functions in T cells, it is still unclear about the underlying mechanism. Here we found a nuclear sensor-Dhx9, was enhanced its expression in effector CD8 T cells. T cell specific deletion of Dhx9 caused an impaired CD8 T cell expansion, memory formation and virus clearance. Mechanically, Dhx9 could directly regulate id2 transcription and in turn control effector CD8 T cell differentiation. Importantly, Dhx9 could bind to Lck protein, mediate Zap70 phosphorylation, and promoting TCR downstream signaling - ERK pathway to protect effector CD8 T cells from apoptosis. The DSRM and DEXDc-Helicase domain is required for Lck binding and Id2 transcription, respectively. Therefore, we revealed a novel regulatory mechanism that innate nuclear sensor regulates T cell fate and function through modulating adaptive pathways.
2020-11-19 | GSE161697 | GEO
Project description:We provide a set of genes that are directly bound by Dhx9 in CD8 T cells from LCMV infected mice.
2020-11-19 | GSE161694 | GEO
Project description:Antigen-specific effector CD8+ T cells deficient in Blimp-1 (Prdm1) do not acquire maximal effector functions, evade terminal differentiation, and more rapidly acquire some hallmark properties of memory CD8+ T cells. In this study, we compared the gene expression profiles of wildtype and Prdm1-/- LCMV-specific effector CD8+ T cells to better understand the molecular mechanisms underlying this striking phenotype. DNA microarray analysis was performed of DbGP33-41 and DbNP396-404 tetramer-positive effector CD8+ T cells FACS-sorted at day 8 post-LCMV infection from four independent samples of either Blimp-1 conditional knockout mice (CKO; Blimp-1flox/flox x GranzymeB-cre+) or wildtype (WT) littermate controls.
2010-08-19 | E-GEOD-17211 | biostudies-arrayexpress
Project description:Innate sensor Dhx9 directly binds to multiple genes related to effector CD8 T cell differentiation
| PRJNA679186 | ENA
Project description:Transcriptome analyses of naive, effector and memory CD8 TCRP1A lymphocytes expressing or not an active form of the transcription factor Stat5. TCRP1A CD8 T lymphocytes were activated by their cognate Ag for 72h to induce their differentiation in effector T cells (TCRP1A eTL 72h: 4 replicates S1, S2, S3, S4). In some samples, an active form of Stat5 was introduced (TCRP1A Stat5ca eTL 72h: 2 replicates S9, S10). These 72h activated T cells were either purified and analyzed directly (samples mentioned above) or injected in congeneic hosts and recovered more than 20 days later from the host spleen and lymph nodes: TCRP1A eTL >d20: 2 replicates– S30, S32; TCRP1A Stat5ca eTL >d20: 4 replicates S11, S12, S13, S14). Naive TCRP1A CD8 T lymphocytes (TCRP1A-naive: 4 replicates S33, S34, S35, S36) are included as controls. TCRP1A CD8 T lymphocytes were activated by anti-CD3/CD28. After 24h, an active form of Stat5 was introduced in activated cells. Culture was continued for another 48h to induce their differentiation in effector T cells. These 72h activated T cells were either directly injected in congeneic hosts and recovered more than 14 days later from the host spleen and lymph nodes: T-BetKO Stat5ca >d14: 3 replicates S39, S40, S41.
2013-09-13 | E-GEOD-26945 | biostudies-arrayexpress
Project description:CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a regenerative program is not completely understood. Here, we have studied antigen-specific assay systems, which revealed that human CD8 T cells not only mediated cytotoxicity, but also promoted bystander fibroblast and epithelial cell activation, leading to the production of tissue regenerative factors such as Amphiregulin (Areg). Tissue remodeling could be inhibited by blocking the epidermal growth factor receptor or the effector cytokines IFN- and TNF. Using single-cell chromatin accessibility and gene expression analysis, we identified a tissue-resident CD8 T cell population in healthy donor skin and adipose tissue with an effector program promoting Areg, TNF and IFNg expression, and a TCR-linkage analysis demonstrated a strong clonal relation between tissue and blood PD1+TIGIT+TOX+ CD8 T cells with tissue remodeling abilities. This regenerative program was also present in anti-cancer associated CD8 populations including chimeric antigen receptor (CAR) CD8 T cells. Once activated, the tissue regenerative program of human CD8 T cells enhanced tumor spheroid, as well as primary liver/bile duct organoid growth. Our findings may help to understand the conflicting CD8 biology in the tumor micromilieu and become relevant for the design of CD8 T-cell therapies for solid tumors.
2023-11-20 | GSE223988 | GEO
Project description:CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a regenerative program is not completely understood. Here, we have studied antigen-specific assay systems, which revealed that human CD8 T cells not only mediated cytotoxicity, but also promoted bystander fibroblast and epithelial cell activation, leading to the production of tissue regenerative factors such as Amphiregulin (Areg). Tissue remodeling could be inhibited by blocking the epidermal growth factor receptor or the effector cytokines IFN- and TNF. Using single-cell chromatin accessibility and gene expression analysis, we identified a tissue-resident CD8 T cell population in healthy donor skin and adipose tissue with an effector program promoting Areg, TNF and IFNg expression, and a TCR-linkage analysis demonstrated a strong clonal relation between tissue and blood PD1+TIGIT+TOX+ CD8 T cells with tissue remodeling abilities. This regenerative program was also present in anti-cancer associated CD8 populations including chimeric antigen receptor (CAR) CD8 T cells. Once activated, the tissue regenerative program of human CD8 T cells enhanced tumor spheroid, as well as primary liver/bile duct organoid growth. Our findings may help to understand the conflicting CD8 biology in the tumor micromilieu and become relevant for the design of CD8 T-cell therapies for solid tumors.
2023-11-20 | GSE223987 | GEO
Project description:During a T cell response, naïve CD8 T cells differentiate into effector cells. Subsequently, a subset of effector cells termed memory precursor effector cells (MPECs) further differentiates into functionally mature memory CD8 T cells. The transcriptional network underlying this carefully scripted process is not well understood. Here, we report that the transcription factor FoxO1 plays an integral role in facilitating effector to memory transition and functional maturation of memory CD4 and CD8 T cells. We find that FoxO1 is not required for differentiation of effector cells, but in the absence of FoxO1, memory CD8 T cells displayed features of scenescence and progressive attrition in polyfunctionality, which in turn led to impared recall responses and poor protective immunity. These data suggest that FoxO1 is essential for active maintenance of functional CD8 T cell memory and protective immunity. Under competing conditions in bone marrow Single-cell suspensions from splenocytes of eight samples WT (control) and FoxO1-/- (experimental) LCMV-immune mice were prepared using standard procedures. CD8 T cells were then isoloated using Thy1.2 (CD90.2) (30-H12) microbeads (Miltenyi Biotec). Cells were then stained with anti-CD8, anti-CD44 and Db/NP396 MHC class I tetramer. Activated (CD8+CD44hi), naive (CD8+CD44lo), and virus-specific CD8 T cells were sorted using FACSAria II instrument (BD Biosciences). The purity of the cells was >95%. Total RNA was extracted from the sorted cells by Trizol Reagent. RNA samples were reverse transcribed and Cy3-labeled cDNAs were hyrbidized to Agilent whole Mouse Genome Oligo Microarrays. Fluorscence signals were detected using Agilent's Microarray Scanner system, data was analyzed using the Rosetta Resolver gene expression data analysis system and genes with a fold change < and p-values <0.01 were identified. Microarray data discussed in the paper is focused on virus-specific memory CD8 T cells from samples WT_Tet_2 vs KO_Tet_2.
2013-06-25 | E-GEOD-45673 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Abstract Paper: CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a tissue regeneration program is poorly understood. Here, antigen-specific assay systems revealed that human CD8 T cells not only mediated cytotoxicity, but also promoted tissue remodeling. Activated CD8 T cells could produce the epidermal growth factor receptor (EGFR)-ligand amphiregulin (AREG) and sensitize epithelial cells for enhanced regeneration potential. Blocking the EGFR or the effector cytokines IFN-γ and TNF could inhibit tissue remodeling. This regenerative program enhanced tumor spheroid and stem-cell-mediated organoid growth. Using single-cell gene expression analysis, we identified an AREG+, tissue-resident CD8 T-cell population in healthy donor skin and adipose tissue with a strong TCR clonal relation to blood PD1+TIGIT+ CD8 T cells with tissue remodeling abilities. These findings may help to understand the complex CD8 biology in tumors and could become relevant for the design of therapeutic T-cell products.
2023-11-20 | GSE223989 | GEO