Gene profiling of the antitumor effects of Cxcl13-positive pancreatic stellate cells in an allogeneic subcutaneous transplantation model.
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ABSTRACT:
PROVIDER: PRJNA1091906 | ENA |
REPOSITORIES: ENA
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Project description:Pancreatic stellate cells are a kind of fibroblasts present in the pancreas and are the cells of origin of cancer-associated fibroblasts. In our previous study, we demonstrated the presence of Cxcl13-positive pancreatic stellate cells as a subpopulation of pancreatic stellate cells. In their genetic profiling, they were predicted to have anti-tumor effects, but their behavior in pancreatic cancer tissue in vivo is unknown. Whole transcriptome analysis was performed to identify genes altered in tumors in which Cxcl13-positive pancreatic stellate cells were allogeneically subcutaneously transplanted with a pancreatic cancer cell line. In addition to the Cxcl13-positive pancreatic stellate cells, tumors transplanted with myofibroblastic pancreatic stellate cells were also subjected to whole transcriptome analysis.
2025-04-30 | GSE262456 | GEO
Project description:Subcutaneous nanotherapy repurposes the immunosuppressive mechanism of rapamycin to enhance allogeneic islet graft viability
| PRJNA757750 | ENA
Project description:Oral rapamycin administration rapamycin is plagued by poor bioavailability and wide biodistribution. Thus, this pleotropic mTOR inhibitor has a narrow therapeutic window, numerous side effects and provides inadequate transplantation protection. Parental formulation was not possible due to rapamycin’s hydrophobicity (log P 4.3). Here, we demonstrate that subcutaneous rapamycin delivery via poly(ethylene glycol)-b-poly(propylene sulfide)(PEG-b-PPS) polymersome (PS) nanocarriers modulates cellular biodistribution of rapamycin to change its immunosuppressive mechanism for enhanced efficacy while minimizing side effects. While oral rapamycin inhibits naïve T cell proliferation directly, subcutaneously administered rapamycin-loaded polymersomes (rPS) instead modulated Ly-6Clow monocytes and tolerogenic semi-mature dendritic cells, with immunosuppression mediated by CD8+ Tregs and rare CD4+ CD8+ double-positive T cells. As PEG-b-PPS PS are uniquely non-inflammatory, background immunostimulation from the vehicle was avoided, allowing immunomodulation to be primarily attributed to rapamycin’s cellular biodistribution. Repurposing mTOR inhibition significantly improved maintenance of normoglycemia in a clinically relevant, MHC-mismatched, allogeneic, intraportal (liver) islet transplantation model. These results demonstrate the ability of engineered nanocarriers to repurpose drugs for alternate routes of administration by rationally controlling cellular biodistribution.
2022-01-01 | GSE182776 | GEO
Project description:SLE is prototypical autoimmune disease driven by pathologic T cell-B cell interactions. Expansion of B cell-helper T cells including T follicular helper (Tfh) and T peripheral helper (Tph) cells is a prominent feature of systemic lupus erythematosus (SLE). Human Tfh and Tph cells characteristically produce high levels of the B cell chemoattractant CXCL13, yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4 T cell phenotypes in SLE patients, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4 T cells. Transcriptomic, epigenetic, and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ Tph/Tfh cell differentiation and promote an IL-22+ phenotype. Type I interferon (IFN), a pathogenic driver of SLE, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ Tph/Tfh cells on a polarization axis opposite from Th22 cells and reveal AHR, JUN, and IFN as key regulators of these divergent T cell states.
2024-07-08 | GSE233050 | GEO
Project description:Expansion of B cell-helper T cells including T follicular helper (Tfh) and T peripheral helper (Tph) cells is a prominent feature of systemic lupus erythematosus (SLE), a prototypical autoimmune disease with broad autoantibody production. Human Tfh and Tph cells are marked by high production of the B cell chemoattractant CXCL13, yet regulation of T cell CXCL13 production and the relationship between a CXCL13+ state and other differentiated T cell states remains largely undefined. Here, we identify a dramatic imbalance in CD4 T cell phenotypes in SLE patients, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4 T cells. Transcriptomic, epigenetic, and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ Tph/Tfh cell differentiation and promote an IL-22+ phenotype. Type I interferon (IFN), a pathogenic driver of SLE, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ Tph/Tfh cells on a polarization axis opposite from Th22 cells and reveal AHR, JUN, and IFN as key regulators of these divergent T cell states.
2024-09-22 | GSE277730 | GEO
Project description:SLE is prototypical autoimmune disease driven by pathologic T cell-B cell interactions. Expansion of B cell-helper T cells including T follicular helper (Tfh) and T peripheral helper (Tph) cells is a prominent feature of systemic lupus erythematosus (SLE). Human Tfh and Tph cells characteristically produce high levels of the B cell chemoattractant CXCL13 yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4 T cell phenotypes in SLE patients, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4 T cells. Transcriptomic, epigenetic, and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ Tph/Tfh cell differentiation and promote an IL-22+ phenotype. Type I interferon (IFN), a pathogenic driver of SLE, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ Tph/Tfh cells on a polarization axis opposite from Th22 cells and reveal AHR, JUN, and IFN as key regulators of these divergent T cell states.
2024-07-08 | GSE252917 | GEO
Project description:SLE is prototypical autoimmune disease driven by pathologic T cell-B cell interactions. Expansion of B cell-helper T cells including T follicular helper (Tfh) and T peripheral helper (Tph) cells is a prominent feature of systemic lupus erythematosus (SLE). Human Tfh and Tph cells characteristically produce high levels of the B cell chemoattractant CXCL13, yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4 T cell phenotypes in SLE patients, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4 T cells. Transcriptomic, epigenetic, and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ Tph/Tfh cell differentiation and promote an IL-22+ phenotype. Type I interferon (IFN), a pathogenic driver of SLE, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ Tph/Tfh cells on a polarization axis opposite from Th22 cells and reveal AHR, JUN, and IFN as key regulators of these divergent T cell states.
2024-07-08 | GSE233048 | GEO
Project description:Purpose: The goal of this study is to characterise the follicular dendritic cells (FDCs) upon antigen-immunocomplex immunisation. Methods: FACS sorting of Live/Death- Podoplanin+ CD31- CD45- CXCL13-TdTomato+ after LN disgregation of CXCL13-CreTdTomato mice. Mice has been previously immunised with antigen-Ics at different time-points. Cells were loaded into 10x Genomics Chromium Platform, and sequenced using Illumina HiSeq 4000. Conclusions: Our study detects previously identified stromal cell populations and shows the heterogeneity present on the FDCs. We detect 3 different FDC clusters.
2023-06-28 | GSE213254 | GEO
Project description:Regulation of T cell CXCL13 production
| PRJNA1085794 | ENA
Project description:Regulation of T cell CXCL13 production
| PRJNA1085795 | ENA