Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA248314 | ENA |
REPOSITORIES: ENA
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Project description:Analysis of the p38 MAPK pathway in regulation of dendritic cells (DCs) differentiation at the gene expression level. Bone marrow cells were cultured with mGM-CSF (20 ng/ml) in the presence of 1.5 mM of SB202190 or 0.1% DMSO. At day 7, semi-adherent cells were collected as immature DCs (iDCs). iDCs were matured by TNF-a (10 ng/ml) and IL-1b (10 ng/ml) for 48 hours. Results showed that p38 MAPK activity in DC progenitor cells acts as an antigen presentation attenuator, and disabling this critical brake during DC differentiation endows DCs with enhanced immunogenicity, which may be useful for the induction of antitumor immune responses. Total RNA was obtained from 2-day-cultured bone marrow cells, iDCs and mature DCs.
2014-05-22 | E-GEOD-57879 | biostudies-arrayexpress
Project description:Analysis of the p38 MAPK pathway in regulation of dendritic cells (DCs) differentiation at the gene expression level. Bone marrow cells were cultured with mGM-CSF (20 ng/ml) in the presence of 1.5 mM of SB202190 or 0.1% DMSO. At day 7, semi-adherent cells were collected as immature DCs (iDCs). iDCs were matured by TNF-a (10 ng/ml) and IL-1b (10 ng/ml) for 48 hours. Results showed that p38 MAPK activity in DC progenitor cells acts as an antigen presentation attenuator, and disabling this critical brake during DC differentiation endows DCs with enhanced immunogenicity, which may be useful for the induction of antitumor immune responses.
2014-05-22 | GSE57879 | GEO
Project description:Dendritic cells (DCs) uniquely direct the adaptive immune response towards activation or inhibition, yet little is known how these opposite programs are regulated at the transcriptional level. Here we applied genome-wide approaches to delineate the molecular function of DC-Specific transCRIPT (DC-SCRIPT/ZNF366), an 11 Zn finger-containing transcription factor potentiating DC-function by limiting IL-10 production. Transcriptome analysis identified DC-SCRIPT to affect expression of genes involved in MAPK signaling, and ChIP-Seq analysis showed binding of DC-SCRIPT to GA-rich enhancers nearby genes encoding MAPK Dual-Specificity Phosphatases (DUSPs). Functional studies demonstrated that DC-SCRIPT-knockdown DCs express much less DUSP4 and exhibit increased phosphorylation of all the three major MAPKs (ERK, JNK and p38). Enhanced ERK signaling in DC-SCRIPT-knockdown DCs led to higher production of the immune-inhibitory cytokine IL-10, which could be reverted by DUSP4 overexpression. These results delineate the molecular mechanism DC-SCRIPT employs to limit IL-10 production in DCs, thereby fine-tuning these professional antigen-presenting cells towards immune activation.
2018-06-19 | GSE78923 | GEO
Project description:In chorioamnionitis (CAM), a major cause of preterm birth (PTB), maternal-fetal inflammatory responses in the decidua and amnio-chorion cause the release of cytokines that elicit cervical ripening, fetal membrane rupture and myometrial activation. We posited that this inflammatory milieu can trigger PTB via inhibited progesterone receptor (PR) expression and increased decidual prostaglandin (PG) production. We found significantly lower decidual cell PR levels in CAM-complicated PTB using immunohistochemistry. Decidual cells (DCs) treated with IL-1β displayed decreased PR expression and significantly increased PGE2 and PGF2α production and COX2 expression. While addition of PGF2α to DC cultures was also found to suppress PR expression, the COX inhibitor, indomethacin, did not reverse IL-1β suppression of PR expression in DC cultures. Although IL-1β treatment activated NF-B, ERK1/2 and p38 MAPK signaling cascades in DCs, only inhibition of ERK1/2 MAPK signaling completely reversed IL-1β suppressed PR levels. These findings suggest that CAM-associated PTB is induced at least in part by IL-1β-mediated functional progesterone withdrawal.
2015-02-11 | GSE65835 | GEO
Project description:Immune checkpoint blockade (ICB) has transformed cancer therapy. Therapeutic efficacy of ICB depends on dendritic cell (DC)-mediated tumor antigen presentation, T-cell priming and activation. However, the relationship between the key transcription factors in DCs and ICB efficacy remains unknown. Here, we discover that ICB reprogramed the interplay between the STAT3 and STAT5 transcriptional pathways in DCs, thereby activating T-cell immunity, and enabling ICB efficacy in cancer patients and tumor bearing mice. Mechanistically, STAT3 competed with STAT5 for JAK interaction, determining the fate of DC function. As STAT3 is often activated in the tumor microenvironment (TME), we designed specific PROTAC degraders of STAT3, SD-36 and SD-2301. Low doses of SD-36 selectively and preferentially degraded STAT3 in DCs and reprogramed the DC transcriptional network toward immunogenicity. Furthermore, SD-36 monotherapy efficiently treated mice bearing large, advanced tumors and ICB resistant tumors without any signs of toxicity. Notably, SD2301 exhibits superior therapeutic efficacy compared to SD-36. Thus, the crosstalk between STAT3 and STAT5 determines DC phenotype in the TME and STAT3-degradation holds promise for cancer immunotherapy.
2025-05-14 | GSE289764 | GEO
Project description:Transcriptome analysis of IFNγ-insensitive DCs IFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg) cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but not in Treg cells resulted in a severe defect in this specific Treg cell subset, leading to exacerbated immune pathology during parasitic infections. Mechanistically, IFNγ-unresponsive DCs failed to produce sufficient amount of IL-27, a cytokine required for optimal T-bet induction in Treg cells. Thus, IFNγ signalling endows DCs with the ability to efficiently control a specific type of T cell immunity through promoting a corresponding Treg cell population. We analyzed saliva from 3 WT DC samples and 3 IFNγR2 KO DC samples isolated from unmanipulated mice. In addition, we analyzed saliva from 3 WT DC samples and 3 IFNγR2 KO DC samples isolated from mixed BM chimeras (WT + IFNgR2KO) day 8 T. gondii infected.
2015-01-01 | E-GEOD-64594 | biostudies-arrayexpress
Project description:Analysis of the specific transcriptional changes on DCs provided by direct pattern recogition receptor (PRR) or IFNAR signaling that are required for DC maturation after poly IC stimulation. Results provide important information about the intricate differentiation process of DC maturation and the importance of type I IFNs for DC immunogenicity. WT/IFNA-/- or WT/PRR-/- mixed-chimera mice were injected with 50 ug Poly-IC i.p. in vivo 4 and 14 hr later, wild type and KO CD11chi CD3- DX5- B220- DCs were FACS sorted based on CD45.2 expression. Total RNA was isolated and expression profile was compared between unstimulated and activated WT and KO DCs.
2013-10-01 | E-GEOD-46478 | biostudies-arrayexpress
Project description:Diabetic patients face an increased risk of developing cataracts, with unclear mechanisms. Our study illuminates these mechanisms by identifying differentially expressed proteins in the lens anterior capsule of diabetic cataract (DC) and age-related cataract patients using quantitative proteomics. We found SH2B1 to be crucial in DC progression. Reduced SH2B1 expression was confirmed through PCR and Western blotting in patient samples, diet-induced obese mice, and high-glucose (HG)-cultured human lens epithelial cells. Under HG conditions, cell proliferation decreased, while migration and apoptosis, alongside changes in Bcl2 and caspase 3 expression, increased. Overexpressing SH2B1 alleviated these changes and influenced the p38 MAPK signaling pathway. This suggests SH2B1 and the p38 MAPK pathway as significant in DC pathogenesis and potential therapeutic targets. Clinically, this could lead to therapies aimed at halting or slowing DC progression.
2025-05-07 | PXD059243 | Pride
Project description:Expression data from dendritic cell subsets derived or sorted from control littermate and CD11c-Cre/BRAFV600E(flox-CA) mice Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by granulomatous lesions containing pathological CD207+ dendritic cells (DCs) with constitutively activated mitogen-activated protein kinase (MAPK) pathway signaling. Approximately 60% of LCH patients harbor somatic BRAFV600E mutations localizing to CD207+ DCs within lesions. However, the mechanisms driving BRAFV600E+ LCH cell accumulation in lesions remain unknown. Here we show that sustained extracellular signal–related kinase activity induced by BRAFV600E inhibits C-C motif chemokine receptor 7 (CCR7)–mediated DC migration, trapping DCs in tissue lesions. Additionally, BRAFV600E increases expression of BCL2-like protein 1 (BCL2L1) in DCs, resulting in resistance to apoptosis. Pharmacological MAPK inhibition restores migration and apoptosis potential in a mouse LCH model, as well as in primary human LCH cells. We also demonstrate that MEK inhibitor-loaded nanoparticles have the capacity to concentrate drug delivery to phagocytic cells, significantly reducing off-target toxicity. Collectively, our results indicate that MAPK tightly suppresses DC migration and augments DC survival, rendering DCs in LCH lesions trapped and resistant to cell death.
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Project description:Vaccine development involves time-consuming and expensive evaluation of candidate vaccines in animal models. As mediators of both innate and adaptive immune responses dendritic cells (DCs) are considered to be highly important for vaccine performance. Here we evaluated in how far the response of DCs to a vaccine in vitro is in line with the immune response the vaccine evokes in vivo. To this end, we investigated the response of murine bone marrow-derived DCs to whole inactivated virus (WIV) and subunit (SU) influenza vaccine preparations. These vaccine preparations were chosen because they differ in the immune response they evoke in mice with WIV being superior to SU vaccine through induction of higher virus-neutralizing antibody titers and a more favorable Th1-skewed response phenotype. To evaluate if in vivo immunogenicity is reflected by DC reactions in vitro we studied the gene expression signature of murine bone-marrow-derived conventional DCs (cDCs) upon stimulation with WIV or SU influenza vaccine or, for reasons of comparison, with live influenza virus. Dendritic cells stimulated with PBS served as a control. Gene expression analysis was performed on samples 4, 12 and 24 hours after the start of stimulation.
2015-02-13 | E-MTAB-3115 | biostudies-arrayexpress