Similar Datasets
Project description:Neuropilin-1(NRP1) is a T cell memory checkpoint limiting long-term anti-tumor immunity
| PRJNA635953 | ENA
Project description:We aimed to evaluate if Lmo4 is directly involved in the generation and preservation of stem cell-like T cells and if adoptively transferred Lmo4-overexpressing pmel-1 CD8+ T cells (which identify the shared melanoma-melanocyte differentiation antigen gp100) are therapeutically effective in mice bearing subcutaneous B16-hgp100 melanomas. Moreover, our purpose was to investigate the mechanisms by which Lmo4 regulates CD8+ T cell differentiation.
2024-07-24 | GSE248171 | GEO
Project description:To compare subpopulations of Treg cells in wild type mice based upon Nrp1 Expression, differentiating nTreg and iTreg Cells were FACS sorted based upon expression of CD4, Foxp3 and expression of Nrp1.
2012-08-30 | E-GEOD-40441 | biostudies-arrayexpress
Project description:Robust CD8+ T cell memory is essential for long-term protective immunity but is often compromised in cancer, where T cell exhaustion leads to loss of memory precursors. Immunotherapy via checkpoint blockade may not effectively reverse this defect, potentially underlying disease relapse. Here we report that mice with a CD8+ T cell-restricted neuropilin-1 (NRP1) deletion exhibited substantially enhanced protection from tumor rechallenge and sensitivity to anti-PD1 immunotherapy, despite unchanged primary tumor growth. Mechanistically, NRP1 cell-intrinsically limited the self-renewal of the CD44+PD1+TCF1+TIM3- progenitor exhausted T cells, which was associated with their reduced ability to induce c-Jun/AP-1 expression on T cell receptor restimulation, a mechanism that may contribute to terminal T cell exhaustion at the cost of memory differentiation in wild-type tumor-bearing hosts. These data indicate that blockade of NRP1, a unique 'immune memory checkpoint', may promote the development of long-lived tumor-specific Tmem that are essential for durable antitumor immunity.
| S-EPMC7442600 | biostudies-literature
Project description:HUVECs transfected with siRNA targeting Neuropilin 1(NRP1) (si-NRP1) or a control non-targeting sequence (si-control) and exposed to unidirectional shear stress (20dyns/cm2), oscillatory flow (5dyn/cm2) or kept in absence of flow.
2023-05-23 | E-MTAB-12191 | biostudies-arrayexpress
Project description:To compare subpopulations of Treg cells in wild type mice based upon Nrp1 Expression, differentiating nTreg and iTreg
2012-08-30 | GSE40441 | GEO
Project description:To understand why cancer vaccine-induced T cells often fail to eradicate tumors, we studied immune responses in mice vaccinated with gp100 peptide emulsified in incomplete Freund's adjuvant (IFA), commonly used in clinical cancer vaccine trials. After gp100 peptide/IFA vaccination, tumor-specific CD8+ T cells (adoptively transferred from gp100-specific TCR-transgenic pmel-1 mice) accumulated not in tumors but at the persisting, antigen-rich vaccination site. Once there, primed T cells became dysfunctional and underwent antigen-driven, IFN-γ and FasL-mediated apoptosis, resulting in systemic hyporesponsiveness to subsequent vaccination. Provision of anti-CD40 antibody, TLR7 agonist and interleukin-2 (covax) reduced T cell apoptosis but did not prevent vaccination site sequestration. A non-persisting vaccine formulation shifted T cell localization towards tumors, inducing superior anti-tumor activity. Short-lived formulation also reduced systemic T cell dysfunction and promoted memory formation, as shown by gene expression profiling and other measures. Persisting peptide/IFA vaccine depots, currently used to vaccinate cancer patients, can induce specific T cell sequestration at vaccination sites followed by dysfunction and deletion; short-lived depot formulations may overcome these limitations and result in greater therapeutic efficacy of peptide-based cancer vaccines. To study the fate of melanoma-specific CD8+ T cells after peptide vaccination, we tracked T cell receptor-transgenic pmel-1 T cells in mice vaccinated with heteroclitic gp100_25-33 peptide emulsified in IFA. Splenic pmel-1 CD8+ T cells were purified at 6 and 21 days after vaccination with either gp100/IFA/covax or gp100/saline/covax, and then their total RNA was extracted and used for comparison by gene expression profiling.
2013-03-02 | E-GEOD-43929 | biostudies-arrayexpress
Project description:Obesity gives rise to metabolic complications by mechanisms that are poorly understood. While chronic inflammatory signaling in adipose tissue is typically associated with metabolic deficiencies linked to excessive weight gain, we identified a subset of NRP1-expressing myeloid cells that accumulate in adipose tissue and protect against obesity and metabolic syndrome. Ablation of NRP1 in macrophages compromised lipid uptake in these cells, which reduced substrates for fatty acid β-oxidation and shifted energy metabolism of these macrophages towards a more inflammatory glycolytic metabolism. Conditional deletion of NRP1 in LysM Cre-expressing cells lead to inadequate adipose vascularization, accelerated weight gain and reduced insulin sensitivity even independent of weight gain. Transfer of NRP1+ hematopoietic cells improved glucose homeostasis, resulting in the reversal of a prediabetic phenotype. Our findings suggest a pivotal role for adipose tissue resident NRP1+-expressing macrophages in driving healthy weight gain and maintaining glucose tolerance.
2018-02-11 | GSE110447 | GEO
Project description:Recent studies have demonstrated that b-catenin in dendritic cells (DCs) serves as a key mediator in promoting both CD4 and CD8 T cell tolerance, although the mechanisms underlying how b-catenin exerts its functions remains incompletely understood. Here we report that activation of b-catenin leads to the up-regulation of inhibitory molecule T-cell immunoglobulin and mucin domain 3 (Tim-3) in type 1 conventional DCs (cDC1s). Using a cDC1-targeted vaccine model with anti-DEC-205 engineered to express the melanoma antigen--human gp100 (anti-DEC-205-hgp100), we demonstrated that CD11c-b-cateninactive mice exhibited impaired cross-priming and memory re-sponses of gp100-specific CD8 T (Pmel-1) cells upon immunization with anti-DEC-205-hgp100. Sin-gle cell RNA sequencing (scRNA-seq) analysis revealed that b-catenin in DCs negatively regulated transcription programs for effector function and proliferation of primed Pmel-1 cells, correlating with suppressed CD8 T cell immunity in CD11c-b-cateninactive mice. Further experiments showed that treating CD11c-b-cateninactive mice with anti-Tim-3 antibody upon anti-DEC-205-hgp100 vac-cination led to restored cross-priming and memory responses of gp100-specific CD8 T cells, sug-gesting that anti-Tim-3 treatment likely synergizes with DC vaccines to improve their efficacy. In-deed, treating B16F10-bearing mice with DC vaccines using anti-DEC-205-hgp100 in combination with anti-Tim-3 treatment resulted in significantly reduced tumor growth, compared to treatment with DC vaccine alone. Taken together, we have identified the b-catenin/Tim-3 axis as a novel mech-anism to inhibit anti-tumor CD8 T cell immunity, and that combination immunotherapy of a DC-targeted vaccine with anti-Tim-3 treatment leads to improved anti-tumor efficacy.
2024-05-02 | GSE263715 | GEO
Project description:Neonates are susceptible to inflammatory disorders such as necrotizing enterocolitis (NEC) due to their immature immune system. The timely appearance of regulatory immune cells in early life contributes to the control of inflammation in neonates, the underlying mechanisms of which remain poorly understood. In this study, we identified a subset of neonatal monocytes characterized with high levels of neuropilin-1 (Nrp1), termed Nrp1 high monocytes. Nrp1high monocytes displayed potent immunosuppressive activity as compared with their Nrp1low counterpart. Nrp1 deficiency in myeloid cells aggravated the severity of NEC, whereas adoptive transfer of Nrp1 highmonocytes led to remission of NEC. Mechanistic studies showed that Nrp1, via binding to its ligand Sema4a, induced intracellular p38-MAPK/mTOR signaling and activated the transcription factor KLF4. KLF4 transactivated Nos2 and enhanced the production of nitric oxide (NO), a key mediator of immunosuppression in monocytes. These observations uncover an important immunosuppressive axis in neonatal monocytes and provide a potential therapeutic strategy for inflammatory disorders in neonates.
2024-04-12 | GSE263510 | GEO