Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA116699 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Increased antigen cross-presentation but impaired cross-priming after activation of PPARγ is mediated by up-regulation of B7H1 Dendritic cells (DCs) are able to take up exogenous antigens and present antigen-derived peptides on MHC class I molecules, a process termed cross-presentation. The mannose receptor (MR), an endocytic receptor expressed on a variety of antigen-presenting cells (APCs), has been demonstrated to target soluble antigens exclusively towards cross-presentation. In this study, we investigated the role of the murine nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor with immunomodulatory properties, in MR-mediated endocytosis and cross-presentation of the model antigen ovalbumin (OVA). We could demonstrate both in vitro and in vivo that activation of PPARγ resulted in increased MR expression, which in consequence led to enhanced MR-mediated endocytosis and elevated cross-presentation of soluble OVA. Concomitantly, activation of PPARγ in DCs induced up-regulation of the co-inhibitory molecule B7H1, which, despite enhanced cross-presentation, caused an impaired activation of naive OVA-specific CD8+ T cells and the induction of T cell tolerance. These data provide a mechanistic basis for the immunomodulatory action of PPARγ which might open new possibilities in development of therapeutical approaches aimed at the control of excessive immune responses, e.g. in T cell-mediated autoimmunity.
2009-06-19 | GSE15616 | GEO
Project description:Increased antigen cross-presentation but impaired cross-priming after activation of PPARγ is mediated by up-regulation of B7H1 Dendritic cells (DCs) are able to take up exogenous antigens and present antigen-derived peptides on MHC class I molecules, a process termed cross-presentation. The mannose receptor (MR), an endocytic receptor expressed on a variety of antigen-presenting cells (APCs), has been demonstrated to target soluble antigens exclusively towards cross-presentation. In this study, we investigated the role of the murine nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor with immunomodulatory properties, in MR-mediated endocytosis and cross-presentation of the model antigen ovalbumin (OVA). We could demonstrate both in vitro and in vivo that activation of PPARγ resulted in increased MR expression, which in consequence led to enhanced MR-mediated endocytosis and elevated cross-presentation of soluble OVA. Concomitantly, activation of PPARγ in DCs induced up-regulation of the co-inhibitory molecule B7H1, which, despite enhanced cross-presentation, caused an impaired activation of naive OVA-specific CD8+ T cells and the induction of T cell tolerance. These data provide a mechanistic basis for the immunomodulatory action of PPARγ which might open new possibilities in development of therapeutical approaches aimed at the control of excessive immune responses, e.g. in T cell-mediated autoimmunity. Comparison of murine mannose receptor negative versus mannose receptor positive bone marrow-derived DCs
2010-05-08 | E-GEOD-15616 | biostudies-arrayexpress
Project description:The cancer-immunity cycle requires cross-presenting dendritic cells (cDC1) that induce T cell-mediated immunity, but therapeutic strategies for enhancing intratumoral cDC1 function are inadequate. We discovered the epigenetic enzyme Carm1 as a selective negative regulator of cancer antigen presentation by cDC1s, but not cDC2s. Carm1 inactivation promoted cDC1 antigen cross-presentation, activation, and accumulation in tumors; and a Carm1 inhibitor enhanced cDC1-mediated priming of T cells by a cancer vaccine. Carm1 inhibition increased chromatin accessibility at BATF3-JUN and RELA sites critical for cDC1 function and activation. Carm1 expression was regulated by TGF-beta, explaining why Carm1 inactivation enhanced intratumoral cDC1 function without altering cDC1 homeostasis. These studies identify Carm1 as a therapeutic target for enhancing the anti-tumor function of murine and human cDC1.
2026-06-30 | GSE300017 | GEO
Project description:The cancer-immunity cycle requires cross-presenting dendritic cells (cDC1) that induce T cell-mediated immunity, but therapeutic strategies for enhancing intratumoral cDC1 function are inadequate. We discovered the epigenetic enzyme Carm1 as a selective negative regulator of cancer antigen presentation by cDC1s, but not cDC2s. Carm1 inactivation promoted cDC1 antigen cross-presentation, activation, and accumulation in tumors; and a Carm1 inhibitor enhanced cDC1-mediated priming of T cells by a cancer vaccine. Carm1 inhibition increased chromatin accessibility at BATF3-JUN and RELA sites critical for cDC1 function and activation. Carm1 expression was regulated by TGF-beta, explaining why Carm1 inactivation enhanced intratumoral cDC1 function without altering cDC1 homeostasis. These studies identify Carm1 as a therapeutic target for enhancing the anti-tumor function of murine and human cDC1.
2026-06-30 | GSE300014 | GEO
Project description:The cancer-immunity cycle requires cross-presenting dendritic cells (cDC1) that induce T cell-mediated immunity, but therapeutic strategies for enhancing intratumoral cDC1 function are inadequate. We discovered the epigenetic enzyme Carm1 as a selective negative regulator of cancer antigen presentation by cDC1s, but not cDC2s. Carm1 inactivation promoted cDC1 antigen cross-presentation, activation, and accumulation in tumors; and a Carm1 inhibitor enhanced cDC1-mediated priming of T cells by a cancer vaccine. Carm1 inhibition increased chromatin accessibility at BATF3-JUN and RELA sites critical for cDC1 function and activation. Carm1 expression was regulated by TGF-beta, explaining why Carm1 inactivation enhanced intratumoral cDC1 function without altering cDC1 homeostasis. These studies identify Carm1 as a therapeutic target for enhancing the anti-tumor function of murine and human cDC1.
2026-06-30 | GSE300012 | GEO
Project description:The cancer-immunity cycle requires cross-presenting dendritic cells (cDC1) that induce T cell-mediated immunity, but therapeutic strategies for enhancing intratumoral cDC1 function are inadequate. We discovered the epigenetic enzyme Carm1 as a selective negative regulator of cancer antigen presentation by cDC1s, but not cDC2s. Carm1 inactivation promoted cDC1 antigen cross-presentation, activation, and accumulation in tumors; and a Carm1 inhibitor enhanced cDC1-mediated priming of T cells by a cancer vaccine. Carm1 inhibition increased chromatin accessibility at BATF3-JUN and RELA sites critical for cDC1 function and activation. Carm1 expression was regulated by TGF-beta, explaining why Carm1 inactivation enhanced intratumoral cDC1 function without altering cDC1 homeostasis. These studies identify Carm1 as a therapeutic target for enhancing the anti-tumor function of murine and human cDC1.
2026-06-30 | GSE300010 | GEO
Project description:The cancer-immunity cycle requires cross-presenting dendritic cells (cDC1) that induce T cell-mediated immunity, but therapeutic strategies for enhancing intratumoral cDC1 function are inadequate. We discovered the epigenetic enzyme Carm1 as a selective negative regulator of cancer antigen presentation by cDC1s, but not cDC2s. Carm1 inactivation promoted cDC1 antigen cross-presentation, activation, and accumulation in tumors; and a Carm1 inhibitor enhanced cDC1-mediated priming of T cells by a cancer vaccine. Carm1 inhibition increased chromatin accessibility at BATF3-JUN and RELA sites critical for cDC1 function and activation. Carm1 expression was regulated by TGF-beta, explaining why Carm1 inactivation enhanced intratumoral cDC1 function without altering cDC1 homeostasis. These studies identify Carm1 as a therapeutic target for enhancing the anti-tumor function of murine and human cDC1.
2026-06-30 | GSE300019 | GEO
Project description:This a model from the article:
A dynamical perspective of CTL cross-priming and regulation: implications for
cancer immunology.
Wodarz D, Jansen VA. Immunol Lett
2003 May 1;86(3):213-27 12706524
,
Abstract:
Cytotoxic T lymphocytes (CTL) responses are required to fight many diseases such
as viral infections and tumors. At the same time, they can cause disease when
induced inappropriately. Which factors regulate CTL and decide whether they
should remain silent or react is open to debate. The phenomenon called
cross-priming has received attention in this respect. That is, CTL expansion
occurs if antigen is recognized on the surface of professional antigen
presenting cells (APCs). This is in contrast to direct presentation where
antigen is seen on the surface of the target cells (e.g. infected cells or tumor
cells). Here we introduce a mathematical model, which takes the phenomenon of
cross-priming into account. We propose a new mechanism of regulation which is
implicit in the dynamics of the CTL: According to the model, the ability of a
CTL response to become established depends on the ratio of cross-presentation to
direct presentation of the antigen. If this ratio is relatively high, CTL
responses are likely to become established. If this ratio is relatively low,
tolerance is the likely outcome. The behavior of the model includes a parameter
region where the outcome depends on the initial conditions. We discuss our
results with respect to the idea of self/non-self discrimination and the danger
signal hypothesis. We apply the model to study the role of CTL in cancer
initiation, cancer evolution/progression, and therapeutic vaccination against
cancers.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Wodarz D, Jansen VA. (2003) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2024-09-02 | BIOMD0000000685 | BioModels
Project description:Plasmacytoid dendritic cells (pDCs) play a crucial role in orchestrating immune responses, especially against viral infections, and have traditionally been well recognized for their ability to produce type I and type III interferons. However, recent discoveries reveal pDCs to be heterogeneous with more complex functions that include antigen uptake, processing, and presentation. We investigated the antigen cross-presentation ability of pDCs and their role in CD8+ T cell priming, a subject of ongoing debate. Utilizing a novel culturing system of CD8+ T cells and autologous pDCs derived from human blood circulating CD34+ hematopoietic stem and progenitor cells (cHSPCs), we demonstrate that pDCs can efficiently prime CD8+ T cells through cross-presentation, thereby contributing to their expansion and cytotoxic activity. The pDCs’ antigen presentation ability is comparable to that of monocyte-derived dendritic cells (moDCs), which are traditionally known for their efficient antigen presentation capacity. Bioinformatic analysis of the primed CD8+ T cells to uncover their transcriptomic profile following priming by pDCs versus moDCs, revealed distinct genetic signatures, indicating that pDCs prime CD8+ T cells differently than cDCs. These findings challenge the traditional view of pDCs as mere IFN-producing cells, highlighting their significant role in antigen presentation and T cell activation.
2025-02-01 | GSE261447 | GEO
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.
2014-05-01 | GSE54089 | GEO