Fgl2 Regulates FcγRIIB+ CD8+ T Cell Responses during Infection
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PROVIDER: PRJNA1201260 | ENA |
REPOSITORIES: ENA
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Project description:Fgl2 Regulates FcγRIIB+ CD8+ T Cell Responses during Infection
| PRJNA1201258 | 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:To analyze wha's the function of anti-FGl2-scFv on T cells, sorted CD8+T cells transfected with empty vector or with anti-FGL2-scFv were processed RNA next generation sequencing
2022-12-12 | GSE218639 | 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: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:Transcription profiles identified 18 cell types, including 9 B cell subsets, 5 T cell subsets, pc cells, monocytes, natural killer (NK) cells, and dc cells. Compared with WT group, the proportion of naive B cells, transitional B cells, marginal B cells, follicular B cells, CD4-T naive, CD8-T naive, CD4-T regulatory subsets, NKT, NK and DC subsets in Fgl2 KO group decreased. The proportion of PCs, CD4-Tem and monocyte subsets increased. Notably, we identified four new B cell subpopulations in the Fgl2 KO group that cannot be classified as classical B cell subpopulations and are therefore named B cell_sp1, B cell_sp2, B cell_sp3, and B cell_sp4.B cell_sp1 subgroup showed dominant clones of IGHA, IGHM and IGHD in the constant region, while the other 3 different subgroups and pc only showed dominant clones of IGHA in the constant region. This suggests that IGHA clones are most abundant and dominant in Fgl2 KO B cells. In addition, we analyzed in detail the number of different BCR heavy chain genes and related VH gene fragments in the Fgl2 KO-specific B cell subpopulation. At the same time, they also highly express Ccl5, Ccl4, Cxcl2, Cxcl10, Slpi, S100a8, S100a9, Fcer1g and IL-1b genes, which are involved in the regulation of immune process and molecular function. In addition, these specific B cells also highly express genes. Such as PDCD1, HAVCR2, CTLA4 and ICOS, suggesting that these B cells are more likely to fail and may not survive for long.
2026-04-08 | GSE275827 | GEO
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