Similar Datasets
Project description:Regulation of TFR cells by Blimp1
| PRJNA599098 | ENA
Project description:Follicular regulatory T (Tfr) cells restrain follicular helper T (Tfh) cell-mediated B cell responses in the germinal center (GC) reaction to optimize humoral immunity while limiting autoimmunity. The immune system partially regulates GC responses by controlling the stepwise differentiation of Tfh cells. Whether Tfr cell development requires sequential developmental stages and how the immune system regulates these processes to control humoral immunity is poorly understood. Here, we used longitudinal sampling of lymphoid organs along with fate mapping and matched single-cell RNASeq/TCRseq to assess developmental dynamics of Tfr cells. We found that Tfr cells undergo dynamic clonal expansion. During this process, Tfr cells also undergo progressive differentiation through progenitor-like, early effector, and late effector stages. Late effector Tfr cells possess inherent instability, with a propensity to lose expression of the transcription factor FoxP3 to become ExTfr cells. ExTfr have unique features and can be redeemed to become suppressive Tfr cells. Acquisition of a Tfh-like transcriptional program in Tfr cells was an intrinsic predictor of progeny instability. Extrinsically, Tfh cells enhanced late effector Tfr cell differentiation by diverting early effector Tfr cells away from a default Blimp1-expressing pathway to a Bcl6-expressing one. Moreover, Tfh induce Tcf7 in Tfr cells which promotes late effector Tfr differentiation. Together, these data indicate that Tfr cells are a dynamic and plastic cell subset, the progressive differentiation of which is controlled at later effector stages by intrinsic and extrinsic programs that work together to provide a negative feedback loop to control humoral immunity.
2025-10-30 | GSE306818 | GEO
Project description:Regulatory T (Treg) cells are required for peripheral tolerance. Recent evidence indicates that Treg cells can adopt specialized differentiation programs in the periphery that are controlled by transcription factors usually associated with T helper differentiation. We demonstrate that expression of the transcription factor Blimp1 defines a population of Treg cells that localize predominantly to mucosal sites and produces IL-10. Blimp1 is required for IL-10 production by these cells and for their tissue homeostasis. A list of differentially expressed genes were identified from this whole-genome expression profiling experiment. Mouse Blimp1 +/gfp and Blimp1 gfp/gfp regulatory T cells were analyzed. Three replicates each.
2011-02-09 | E-GEOD-27143 | biostudies-arrayexpress
Project description:Follicular regulatory T (Tfr) cells restrain follicular helper T (Tfh) cell-mediated B cell responses in the germinal center (GC) reaction to optimize humoral immunity while limiting autoimmunity. The immune system partially regulates GC responses by controlling the stepwise differentiation of Tfh cells. Whether Tfr cell development requires sequential developmental stages and how the immune system regulates these processes to control humoral immunity is poorly understood. Here, we used longitudinal sampling of lymphoid organs along with fate mapping and matched single-cell RNASeq/TCRseq to assess developmental dynamics of Tfr cells. We found that Tfr cells undergo dynamic clonal expansion. During this process, Tfr cells also undergo progressive differentiation through progenitor-like, early effector, and late effector stages. Late effector Tfr cells possess inherent instability, with a propensity to lose expression of the transcription factor FoxP3 to become ExTfr cells. ExTfr have unique features and can be redeemed to become suppressive Tfr cells. Acquisition of a Tfh-like transcriptional program in Tfr cells was an intrinsic predictor of progeny instability. Extrinsically, Tfh cells enhanced late effector Tfr cell differentiation by diverting early effector Tfr cells away from a default Blimp1-expressing pathway to a Bcl6-expressing one. Moreover, Tfh induce Tcf7 in Tfr cells which promotes late effector Tfr differentiation. Together, these data indicate that Tfr cells are a dynamic and plastic cell subset, the progressive differentiation of which is controlled at later effector stages by intrinsic and extrinsic programs that work together to provide a negative feedback loop to control humoral immunity.
2025-10-30 | GSE307004 | GEO
Project description:To clarify the potential BLIMP1 downstream target regulating PD-L1 expression, we performed proteomics analysis using BLIMP1 Hep3B cells and control cells. Proteomics analysis revealed that SPI1 may serve as a pivotal transcriptional factor that enhances PD-L1 expression by acting as a downstream effector of BLIMP1.
2022-11-23 | PXD037621 | Pride
Project description:Blimp1 is an essential regulator of plasma cells. Here we studied its functions in early plasmablast differentiation by identifying regulated Blimp1 target genes. Blimp1 promoted plasmablast migration and adhesion by controlling many genes involved in these processes. It repressed several transcription factor genes and Aicda, thus silencing B-cell-specific gene expression, antigen presentation and class switch recombination in plasmablasts. It also directly activated genes, leading to increased expression of the plasma cell regulator IRF4 and proteins involved in immunoglobulin secretion. Blimp1 strongly induced immunoglobulin gene transcription by controlling the activity of Igh and Igk 3’ enhancers and regulated the posttranscriptional switch of expression from the membrane-bound to secreted immunoglobulin heavy-chain by activating Ell2. Notably, Blimp1 recruited chromatin-remodeling and histone-modifying complexes to regulate its target gene. Hence, many essential functions of plasma cells are under Blimp1 control.
2015-12-01 | GSE71698 | GEO
Project description:Follicular regulatory T cells (TFR) are a major cellular source of negative regulation of GC antibody responses. Blimp1 is expressed by the majority of TFR cells within B cell follicles during immune responses, as well as by other tissue-specific subsets of effector Treg (eTreg). However, the potential impact of FoxP3-specific Blimp1 deletion on TFR differentiation and suppressive activity has not been evaluated. To better understand the role of Blimp1 in regulation of TFR differentiation and function, we profiled the differential gene expression in Blimp1-deficient TFR cells compared to WT control TFR cells.
2019-11-21 | GSE101611 | GEO
Project description:Regulatory T (Treg) cells are required for peripheral tolerance. Recent evidence indicates that Treg cells can adopt specialized differentiation programs in the periphery that are controlled by transcription factors usually associated with T helper differentiation. We demonstrate that expression of the transcription factor Blimp1 defines a population of Treg cells that localize predominantly to mucosal sites and produces IL-10. Blimp1 is required for IL-10 production by these cells and for their tissue homeostasis. A list of differentially expressed genes were identified from this whole-genome expression profiling experiment.
2011-02-09 | GSE27143 | GEO
Project description:As a part of a modelling experiment for transcriptional control of mouse primordial germ cell specification, the transcription factor BLIMP1 was transiently expressed in the mouse p19 embryonal carcinoma cell line and its genome wide binding sites were defined using ChIPseq.
2013-07-17 | E-MTAB-1599 | biostudies-arrayexpress
Project description:Expression profiling of Prdm1 mutant E9.5 placenta was performed using Illumina whole genome V2 arrays. The hypothesis tested in the present study was that Blimp1 regulates the transcription of key genes involved in trophoblast differentiation. We demonstrate that the invading SpA-TGCs display robust Blimp1 expression and Blimp1 functional loss selectively disrupts specification of this discrete TGC sub-type. Transcriptional profiling experiments identified additional SpA-TGC lineage restricted marker genes that potentially regulate placental morphogenesis.
2012-07-24 | GSE39584 | GEO