De novo methylation enforces long-term lineage-specific programing of TFH and TH1 memory cells [WGBS]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE168398 | GEO | 2025/12/01
REPOSITORIES: GEO
Dataset's files
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| GSE168398_RAW.tar | Raw | |||
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Project description:In this study, we sought to distinguish phenotypically and functionally distinct virus-specific effector CD4 T cell subsets that form during acute lymphocytic choriomeningitis virus (LCMV) infection and to examine their ability to develop into memory T cells. To further characterize the effector subsets and identify genetic pathways and transcription factors involved in their differentiation, we performed genome-wide gene expression profiling of the three day 8 effector cell populations: (1) PSGL1hi Ly6Chi, (2) PSGL1hi Ly6Clo and (3) PSGL1lo Ly6Clo Smarta CD4 T cells along with (4) day 60 memory PSGL1hi and (5) naïve Smarta CD4 T cells using Illumina BeadChips. Results of this microarray confirmed the validity of our phenotyping by flow cytometry in many ways and showed distinct gene signatures for the three effector subsets. DNA microarray analysis was performed on two or three independent samples of five different Smarta CD4 T cell populations: (1) naïSGL1lo, (3) day 8 PSGL1hi Ly6Clo, (4) day 8 PSGL1hi Ly6Clo and (5) day 60 PSGL1hi memory cells.
2011-10-04 | E-GEOD-32596 | biostudies-arrayexpress
Project description:In this study, we sought to distinguish phenotypically and functionally distinct virus-specific effector CD4 T cell subsets that form during acute lymphocytic choriomeningitis virus (LCMV) infection and to examine their ability to develop into memory T cells. To further characterize the effector subsets and identify genetic pathways and transcription factors involved in their differentiation, we performed genome-wide gene expression profiling of the three day 8 effector cell populations: (1) PSGL1hi Ly6Chi, (2) PSGL1hi Ly6Clo and (3) PSGL1lo Ly6Clo Smarta CD4 T cells along with (4) day 60 memory PSGL1hi and (5) naïve Smarta CD4 T cells using Illumina BeadChips. Results of this microarray confirmed the validity of our phenotyping by flow cytometry in many ways and showed distinct gene signatures for the three effector subsets.
2011-10-05 | GSE32596 | GEO
Project description:Following viral clearance, antigen-specific CD4+ T cells contract and form a pool of distinct Th1 and Tfh memory cells that possess unique epigenetic programs, allowing them to rapidly recall their specific effector functions upon rechallenge. DNA methylation programing mediated by the methylcytosine dioxygenase Tet2 contributes to balancing Th1 and Tfh cell differentiation during acute viral infection, however the role of Tet2 in CD4+ T cell memory formation and recall is unclear. Using adoptive transfer models of antigen-specific WT andTet2KO CD4+ T cells, we find that Tet2 is required for full commitment of CD4+ T cells to the Th1 lineage and that in the absence of Tet2, memory cells preferentially recall a Tfh like phenotype with enhanced expansion upon secondary challenge. These findings demonstrate an important role for Tet2 in enforcing lineage commitment and programing proliferation potential, and highlight the potential of targeting epigenetic programing to enhance adaptive immune responses.
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Project description:CD4 T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for longlived antibody responses. However, it remains unclear whether there are CD4+ memory T cells committed to the Tfh lineage after antigen clearance. Using adoptive transfer of antigen-specific memory CD4+ subpopulations (based on CXCR5 and Ly6c expression)in the LCMV infection model, we found that there are distinct memory CD4+ T cell populations with commitment to the Tfh and Th1 lineages. Our conclusions are based on gene expression profiles, epigenetic studies and phenotypic and functional analysis. The gene expression profiles of virus-specific CD4 T cell subets at effector and memory stages is presented here. The SMARTA TCR transgenic / adptive transfer system was used to identify and sort subsets of antigen-specific CD4 T cells (based on their expression of Ly6c and CXCR5) elicited after acute infection with LCMV (Arm).
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Project description:CD4+ memory T cells play a pivatol role in mediating long-term immunity and therefore are an important target in vaccine development. Multiple functionally distinct helper CD4+ T cell subsets can arise in response to a single invading pathogen, complicating the identification of rare memory CD4+ T cells. Here we found that expression of Id3, an inhibitor of E protein transcription factors, identified a population of cells within both the CD4+ Tfh and Th1 helper lineages that exhibited memory potential in response to secondary infection. Notably, a subset of Th1 memory cells expressing Id3 exhibited enhanced expansion upon response to pathogen, generating both Th1 and Tfh secondary effector cell populations, and displayed enrichment of key molecules associated with memory potential when compared to Id3lo Th1 cells. Thus, Id3 expression serves as an important marker of multipotent memory CD4+ T cells.
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Project description:CD4+ memory T cells play a pivatol role in mediating long-term immunity and therefore are an important target in vaccine development. Multiple functionally distinct helper CD4+ T cell subsets can arise in response to a single invading pathogen, complicating the identification of rare memory CD4+ T cells. Here we found that expression of Id3, an inhibitor of E protein transcription factors, identified a population of cells within both the CD4+ Tfh and Th1 helper lineages that exhibited memory potential in response to secondary infection. Notably, a subset of Th1 memory cells expressing Id3 exhibited enhanced expansion upon response to pathogen, generating both Th1 and Tfh secondary effector cell populations, and displayed enrichment of key molecules associated with memory potential when compared to Id3lo Th1 cells. Thus, Id3 expression serves as an important marker of multipotent memory CD4+ T cells.
2022-07-01 | GSE175740 | GEO
Project description:Differentiation of CD4+T-cells into effector subsets is a critical component of the adaptive immune system and an incorrect response can lead to autoimmunity or immune deficiency. Cellular differentiation including T-cell differentiation is accompanied by large-scale epigenetic remodeling, including changes in DNA methylation at key regulators of T-cell differentiation. The TET family of enzymes were recently shown to be able to catalyse methylated cytosine (5mC) into 5-hydroxymethylcytosine (5hmC) enabling a pathway of active removal of DNA methylation. Here, we characterize 5hmC, 5mC and transcriptional dynamics during human CD4+T-cell polarisation in a time series approach and relate these changes to profiles in ex-vivo CD4+memory subsets. We observed large-scale remodelling during early CD4+T-cell differentiation which was predictive of subsequent changes during late time points, these changes were also related to disease associated regions which we show can act as functional regulatory elements. This dataset was designed to assess how gene expression changes over time during human CD4+T-cell polarization towards Th1 and Th2. Gene expression was assessed in relationship to 5hmC and DNA methylation levels and changes (see data series), we observed characteristic gene expression for the specific time points and stimuli or cell type and the expression was correlated with gene body 5hmC as well as anticorrelated with promoter DNA methylation levels. This submission contains data from transcription profiling by array of human CD4+T-cells, Th1/Th2 polarized time-series and primary memory subsets. It is part of series containing 5hmC and DNA methylation profiling of the same samples. See related experiments E-MTAB-4685, E-MTAB-4686, E-MTAB-4688, E-MTAB-4689.
2016-07-11 | E-MTAB-4687 | biostudies-arrayexpress
Project description:Tet2-mediated demethylation is a key component of epigenetic programing that promotes lineage specific gene expression and contributes to cellular differentiation and function. While the differentiation of CD4+ T cell subsets has been studied extensively, the epigenetic programs that regulate these processes remain unclear. We report that Tet2 acts to restrict the differentiation of T follicular helper (Tfh) cells in CD4+ T cells responding to viral infection. Tet2-deficient CD4+ T cells preferentially differentiated into highly functional germinal center (GC) Tfh cells that provided enhanced help for B cell responses. Using genome-wide expression and methylation analyses combined with Foxo1 ChIPseq analysis, we found that Tet2 coordinates with multiple transcription factors, including Foxo1, to mediate the demethylation and expression of their target genes following activation.
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Project description:Tet2-mediated demethylation is a key component of epigenetic programing that promotes lineage specific gene expression and contributes to cellular differentiation and function. While the differentiation of CD4+ T cell subsets has been studied extensively, the epigenetic programs that regulate these processes remain unclear. We report that Tet2 acts to restrict the differentiation of T follicular helper (Tfh) cells in CD4+ T cells responding to viral infection. Tet2-deficient CD4+ T cells preferentially differentiated into highly functional germinal center (GC) Tfh cells that provided enhanced help for B cell responses. Using genome-wide expression and methylation analyses combined with Foxo1 ChIPseq analysis, we found that Tet2 coordinates with multiple transcription factors, including Foxo1, to mediate the demethylation and expression of their target genes following activation.
2022-06-15 | GSE182940 | GEO
Project description:Tet2-mediated demethylation is a key component of epigenetic programing that promotes lineage specific gene expression and contributes to cellular differentiation and function. While the differentiation of CD4+ T cell subsets has been studied extensively, the epigenetic programs that regulate these processes remain unclear. We report that Tet2 acts to restrict the differentiation of T follicular helper (Tfh) cells in CD4+ T cells responding to viral infection. Tet2-deficient CD4+ T cells preferentially differentiated into highly functional germinal center (GC) Tfh cells that provided enhanced help for B cell responses. Using genome-wide expression and methylation analyses combined with Foxo1 ChIPseq analysis, we found that Tet2 coordinates with multiple transcription factors, including Foxo1, to mediate the demethylation and expression of their target genes following activation.
2022-06-15 | GSE183316 | GEO