Opposing roles of E2A and Id3 that orchestrate and enforce the naive T cell fate
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE30518 | GEO | 2011/07/31
SECONDARY ACCESSION(S): PRJNA143293
REPOSITORIES: GEO
Similar Datasets
Project description:It is established that E2A and its antagonist, Id3, modulate developmental progression at the pre-TCR and TCR checkpoints. Here we show at a global scale how E2A promotes commitment to the T cell lineage and how pre-TCR mediated signalling affects E2A genome-wide occupancy. We find aberrant development of CD4 memory-like and TFH-like cells, T-B cell conjugates and, remarkably, B cell follicles in Id3-/-thymi. We also find that Id3-/-CD4 splenocytes exhibit increased numbers of TFH-like cells. We propose a model in which Id3 modulates the naive versus effector/memory cell fate. Collectively, these data show how E2A acts globally to orchestrate T-lineage development and that Id3 antagonizes E2A activity beyond the pre-TCR checkpoint to enforce the naive T cell fate. ChIP-Seq was performed in thymocytes isolated from either untreated Rag2-/-mice (DN3 cells) or Rag2-/- mice injected with anti-CD3e antibody (DN4 cells). ChIP used antibodies against either E2A or H3K4me1.
2011-07-31 | E-GEOD-30518 | biostudies-arrayexpress
Project description:Id proteins have been shown to promote the differentiation of conventional αβ and γδT cells, and to suppress the expansion of invariant Natural Killer T (iNKT) cells and innate-like γδNKT within their respective cell lineages. However, it remains to be determined whether Id proteins regulate lineage specification in developing T cells that give rise to these distinct cell fates. Here we report that in the absence of Id2 and Id3 proteins, E2A prematurely activates genes critical for the iNKT cell lineage prior to TCR expression. Lack of Id proteins also promotes a biased TCR rearrangement in favor of iNKT cell fate prior to selection at the CD4+CD8+ double positive (DP) stage. Enhanced iNKT development in Id3-deficient mice lacking γδNKT cells suggests that Id3 regulates the lineage competition between these populations. RNA-Seq analysis establishes E2A as the transcriptional regulator of both iNKT and γδNKT development. In the absence of pre-TCR signaling, Id2/Id3 deletion gives rise to a large population of iNKT cells and a unique innate-like DP population, despite the block in conventional αβ T cell development. The transcriptional profile of these unique DP cells reflects enrichment of innate-like signature genes, including PLZF (Zbtb16) and Granzyme A (Gzma). Results from these genetic models and genome-wide analyses suggest that Id proteins suppress E2A-driven innate-like T cell programs prior to TCR selection to enforce predominance of conventional T cells.
2018-01-23 | GSE89848 | GEO
Project description:Id proteins have been shown to promote the differentiation of conventional αβ and γδT cells, and to suppress the expansion of invariant Natural Killer T (iNKT) cells and innate-like γδNKT within their respective cell lineages. However, it remains to be determined whether Id proteins regulate lineage specification in developing T cells that give rise to these distinct cell fates. Here we report that in the absence of Id2 and Id3 proteins, E2A prematurely activates genes critical for the iNKT cell lineage prior to TCR expression. Lack of Id proteins also promotes a biased TCR rearrangement in favor of iNKT cell fate prior to selection at the CD4+CD8+ double positive (DP) stage. Enhanced iNKT development in Id3-deficient mice lacking γδNKT cells suggests that Id3 regulates the lineage competition between these populations. RNA-Seq analysis establishes E2A as the transcriptional regulator of both iNKT and γδNKT development. In the absence of pre-TCR signaling, Id2/Id3 deletion gives rise to a large population of iNKT cells and a unique innate-like DP population, despite the block in conventional αβ T cell development. The transcriptional profile of these unique DP cells reflects enrichment of innate-like signature genes, including PLZF (Zbtb16) and Granzyme A (Gzma). Results from these genetic models and genome-wide analyses suggest that Id proteins suppress E2A-driven innate-like T cell programs prior to TCR selection to enforce predominance of conventional T cells.
2018-01-23 | GSE89847 | GEO
Project description:Id proteins have been shown to promote the differentiation of conventional αβ and γδT cells, and to suppress the expansion of invariant Natural Killer T (iNKT) cells and innate-like γδNKT within their respective cell lineages. However, it remains to be determined whether Id proteins regulate lineage specification in developing T cells that give rise to these distinct cell fates. Here we report that in the absence of Id2 and Id3 proteins, E2A prematurely activates genes critical for the iNKT cell lineage prior to TCR expression. Lack of Id proteins also promotes a biased TCR rearrangement in favor of iNKT cell fate prior to selection at the CD4+CD8+ double positive (DP) stage. Enhanced iNKT development in Id3-deficient mice lacking γδNKT cells suggests that Id3 regulates the lineage competition between these populations. RNA-Seq analysis establishes E2A as the transcriptional regulator of both iNKT and γδNKT development. In the absence of pre-TCR signaling, Id2/Id3 deletion gives rise to a large population of iNKT cells and a unique innate-like DP population, despite the block in conventional αβ T cell development. The transcriptional profile of these unique DP cells reflects enrichment of innate-like signature genes, including PLZF (Zbtb16) and Granzyme A (Gzma). Results from these genetic models and genome-wide analyses suggest that Id proteins suppress E2A-driven innate-like T cell programs prior to TCR selection to enforce predominance of conventional T cells.
2018-01-23 | GSE100601 | GEO
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 | GSE175742 | GEO
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 | GSE175741 | GEO
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:Follicular helper T (Tfh) are a subset of CD4+ T helper cells that provide help to germinal center B cells and mediate the development of long-lived humoral immunity. Tfh cells dysregulation is associated with several major autoimmune diseases. Although recent studies showed Tfh cells differentiation is controlled by the transcription factor Bcl6, cytokines and cell-cell signals, limited information is available on the proteome and post-translational modifications (PTM) of proteins in human Tfh cells. In this study, using TMT labeling technique, antibody-based affinity enrichment and high-resolution LC-MS/MS analysis, we investigated quantitative proteome and acetylome in human naive CD4+ T cells and in vitro induced Tfh (iTfh) cells. In total, we identified 802 up-regulated proteins and 598 down-regulated proteins at the threshold of 1.5 folds in iTfh cells compared to naive CD4+ T cells. With the aid of intensive bioinformatics, biological process, cellular compartment, molecular function, KEGG pathway and protein-protein interaction of these differentially expressed proteins were revealed. Moreover, our acetylome data showed that 22 lysine acetylated proteins are up-regulated and 26 lysine acetylated proteins are down-regulated in iTfh cells compared to the naive CD4+ T cells, among which 11 differentially acetylated lysine residues in core histone were identified, indicating proteins acetylation and epigenetic mechanism are involved in regulating Tfh cells differentiation. These data provide a significant resource for studies of Tfh differentiation and normal and perturbed Tfh cell function.
2021-03-19 | PXD008563 | Pride
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).
2013-04-22 | E-GEOD-43863 | biostudies-arrayexpress
Project description:Tight control of follicular helper T(Tfh) cells is required for optimal maturation of the germinal center (GC) response. The molecular mechansims controlling Tfh cell differentiation remain incompletely understood. Here we sought to to identfiy miRNAs that might regulate Tfh cell development and/or function. To identfiy miRNAs that are differentially expressed in Tfh cells, we performed Agilent microRNA microarray analysis comparing Tfh cells with the other main T cell subsets (naive T cells, non-Tfh effector or non-Tfh memory T cells, CD57+ Tfh cells and CD57- Tfh cells). RNA was extracted from 4 separate human tonsils (biological replicates) using mirVANA RNA isolation kit (Ambion) according to the manufacturerM-bM-^@M-^Ys protocol. Each biological sample was analysed individually. Live lymphocytes were sorted based on negative 7AAD staining, and thefollowing four subsets were purified: Naive T cells (CD4+ CD45RO-); CD57+ Tfh cells (CD4+ CD45RO+ PD-1_high CXCR5_high CD57+); CD57- Tfh cells (CD4+ CD45RO+ PD-1_high CXCR5_high CD57-) and non-Tfh effector or memory T cells (CD4+ CD45RO+ PD-1_neg CXCR5_neg). RNA quantity and quality was determined using a Nanodrop 1000 and an Agilent 2100 Bioanalyzer respectively. Hybridization on Agilent Human miRNA Microarray (V1) Kit, 8x15K and was performed at The Ramaciotti Center for Genomics (University of New South Wales, Australia). The mean of 3-4 biological replicates from each population of each population were calculated and values were plotted using Prism.
2015-01-10 | E-GEOD-64833 | biostudies-arrayexpress