Fgl2 Regulates FcγRIIB+ CD8+ T Cell Responses during Infection
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ABSTRACT:
PROVIDER: PRJNA1201258 | ENA |
REPOSITORIES: ENA
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Project description:Fgl2 Regulates FcγRIIB+ CD8+ T Cell Responses during Infection
| PRJNA1201260 | ENA
Project description:The regulatory circuits dictating CD8+ T cell responsiveness vs. exhaustion during anti-tumor immunity are incompletely understood. Here, we report that tumor-infiltrating antigen-specific PD-1+ TCF-1- CD8+ T cells express the immunosuppressive cytokine Fgl2. Conditional deletion of Fgl2 from antigen-specific CD8+ T cells prolonged CD8+ T cell persistence, decreased phenotypic and transcriptomic signatures of T cell exhaustion, and improved tumor control. Melanoma patients who died of their disease exhibited increased expression of Fgl2 in tumor-infiltrating CD8+ T cells as compared to those who survived. PD-1+CD8+ T cell-derived Fgl2 also negatively regulated virus-specific T cell responses in a model of chronic viral infection. Mechanistically, the enhanced responsiveness of Fgl2-deficient CD8+ T cells is underpinned by the interaction of Fgl2 with CD8+ T cell-expressed FcγRIIB, ligation of which results in caspase 3/7-mediated apoptosis. These data illuminate a novel cell-autonomous regulatory axis by which PD-1+ CD8+ T cell responses are regulated in vivo.
2024-01-05 | GSE252556 | GEO
Project description:Memory T cells provide immunity against pathogen reinvasion, but mechanisms of their long-term maintenance is unclear. Here we show that mice with the deletion of the transcription factor Foxo1 in activated CD8+ T cells had defective secondary but not primary responses to Listeria monocytogenes infection. Compared to short-lived effector T cells, memory precursor effector T cells expressed higher amounts of Foxo1 that promoted their generation and maintenance. Gene expression profiling and chromatin immunoprecipitation sequencing experiments revealed the chemokine receptor CCR7 and the transcription factor TCF1 as novel Foxo1-bound target genes with critical functions in memory T cell trafficking and transcriptional regulation. These findings demonstrate that Foxo1 is selectively incorporated into the genetic program that regulates memory but not effector CD8+ T cell responses to infection. CD8+ T cells were isolated from wild-type or Foxo1tagBirA mice in which Foxo1 is endogenously biotinylated. Foxo1 binding targets in CD8+ cells were identified by using Foxo1 antibody- and Streptavidin- ChIP-Seq approaches.
2013-05-16 | E-GEOD-46943 | biostudies-arrayexpress
Project description:Memory T cells provide immunity against pathogen reinvasion, but mechanisms of their long-term maintenance is unclear. Here we show that mice with the deletion of the transcription factor Foxo1 in activated CD8+ T cells had defective secondary but not primary responses to Listeria monocytogenes infection. Compared to short-lived effector T cells, memory precursor effector T cells expressed higher amounts of Foxo1 that promoted their generation and maintenance. Gene expression profiling and chromatin immunoprecipitation sequencing experiments revealed the chemokine receptor CCR7 and the transcription factor TCF1 as novel Foxo1-bound target genes with critical functions in memory T cell trafficking and transcriptional regulation. These findings demonstrate that Foxo1 is selectively incorporated into the genetic program that regulates memory but not effector CD8+ T cell responses to infection. Wild-type and GzmB-cre Foxo1fl/fl CD27hiKLRG1lo OT-I T cells were isolated by FACS sorting at 7 days post LM-OVA infection. RNA was prepared with the miRNeasy kit according to the manufacturer’s instructions (Qiagen). RNA amplification, labeling and hybridization to Mouse 430 2.0 Array chips (Affymetrix) were carried out at the Genomics Core Facility of Memorial Sloan-Kettering Cancer Center.
2013-05-16 | E-GEOD-46942 | biostudies-arrayexpress
Project description:CD8+ T cell differentiation has been associated with changes in the expression of long noncoding RNA (lncRNAs). Yet, which and how lncRNAs regulate CD8+ T cell responses following infection in vivo remain incompletely understood. We performed deep RNA-seq to map the lncRNA expression landscape of CD8+ T cell subsets during infection and generated lncRNA knockout mouse models to evaluate the in vivo relevance of six lncRNAs. We identified the enhancer lncRNA Rroid2 to regulate effector CD8+ T cell function as well as effector-to-memory differentiation. Rroid2-deficient mice displayed increased CD44dim Foxp3+ regulatory T cells while the development of other immune cells, such as natural killer cells, was not affected. In CD8+ T cells, Rroid2 deficiency resulted in a fine-tuned downregulation of transcription factors Id2 and T-bet and impaired effector CD8+ T cell proliferation and cytotoxicity as well as memory CD8+ T cell generation and recall responses. In contrast to Id2, Rroid2 deficiency affected both KLRG1+ and KLRG1- effector CD8+ T cells. Taken together, Rroid2 represents a key regulatory layer that controls CD8+ T cell responses to pathogens.
2025-12-09 | GSE286902 | GEO
Project description:UTX constrains antiviral CD8+ T cell responses during chronic virus infection
| PRJNA601463 | ENA
Project description:HDAC1 regulates effector CD8+ T cell differentiation during chronic viral infection
| PRJNA1132170 | ENA
Project description:Memory T cells provide immunity against pathogen reinvasion, but mechanisms of their long-term maintenance is unclear. Here we show that mice with the deletion of the transcription factor Foxo1 in activated CD8+ T cells had defective secondary but not primary responses to Listeria monocytogenes infection. Compared to short-lived effector T cells, memory precursor effector T cells expressed higher amounts of Foxo1 that promoted their generation and maintenance. Gene expression profiling and chromatin immunoprecipitation sequencing experiments revealed the chemokine receptor CCR7 and the transcription factor TCF1 as novel Foxo1-bound target genes with critical functions in memory T cell trafficking and transcriptional regulation. These findings demonstrate that Foxo1 is selectively incorporated into the genetic program that regulates memory but not effector CD8+ T cell responses to infection.
2013-05-16 | GSE46942 | GEO
Project description:Memory T cells provide immunity against pathogen reinvasion, but mechanisms of their long-term maintenance is unclear. Here we show that mice with the deletion of the transcription factor Foxo1 in activated CD8+ T cells had defective secondary but not primary responses to Listeria monocytogenes infection. Compared to short-lived effector T cells, memory precursor effector T cells expressed higher amounts of Foxo1 that promoted their generation and maintenance. Gene expression profiling and chromatin immunoprecipitation sequencing experiments revealed the chemokine receptor CCR7 and the transcription factor TCF1 as novel Foxo1-bound target genes with critical functions in memory T cell trafficking and transcriptional regulation. These findings demonstrate that Foxo1 is selectively incorporated into the genetic program that regulates memory but not effector CD8+ T cell responses to infection.
2013-05-16 | GSE46943 | GEO
Project description:Latent viral infections rely on a precise coordination of the immune response to control sporadic viral reactivation. CD8+ T cells play a crucial role in controlling viral latency by generating diverse memory responses in an epitope-specific manner. Among these distinct responses, conventional and inflationary memory responses have been described during herpesvirus infections. Using a newly generated T cell receptor transgenic mouse strain, we investigated the transcriptomic and epigenetic remodeling of distinct epitope-specific CD8+ T cells during cytomegalovirus (CMV) infection across tissues at both population and single-cell levels. Our findings reveal that whereas the transcriptomic and epigenetic landscape of conventional and inflationary memory responses diverge in the spleen and liver, these molecular programs converge in the salivary gland, a site of CMV persistence. Thus, we provide evidence that the dynamics of memory CD8+ T cell responses are nuanced and exquisitely distinct between tissues.
2025-05-01 | GSE291432 | GEO