Expression data from wt, Lkb1 conditional knock out and LPS treated DC
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE117286 | GEO | 2018/10/29
REPOSITORIES: GEO
Similar Datasets
Project description:Expression data from wt, Lkb1 conditional knock out and LPS treated DC
| PRJNA481663 | ENA
Project description:Liver Kinase B1 (LKB1) plays a key role in cellular metabolism by controlling AMPK activation. However, its function in dendritic cell (DC) biology has not been addressed. Here, we find that LKB1 functions as a critical brake on DC immunogenicity, and when lost, leads to reduced mitochondrial fitness and increased maturation, migration, and T cell priming of peripheral DCs. Concurrently, loss of LKB1 in DCs enhances their capacity to promote output of regulatory T cells (Tregs) from the thymus, which dominates the outcome of peripheral immune responses, as suggested by increased resistance to asthma and higher susceptibility to cancer in CD11cΔLKB1 mice. Mechanistically, we find that loss of LKB1 specifically primes thymic CD11b+ DCs to facilitate thymic Treg development and expansion, which is independent from AMPK signalling, but dependent on mTOR and enhanced phospholipase C β1-driven CD86 expression. Together, our results identify LKB1 as a critical regulator of DC-driven effector T cell and Treg responses both in the periphery and the thymus.
2020-05-07 | GSE149941 | GEO
Project description:Loss of LKB1 leads to aberrant DC maturation and production of cytokines and immunoregulatory molecules. DCs (n = 7 per genotype) were isolated from the spleen, and CD25+CD4+ Tregs (n = 4 for WT, n = 3 for LKB1ΔDC mice) were isolated from the spleen and peripheral lymph nodes of WT and LKB1ΔDC mice.
2019-04-16 | GSE128474 | GEO
Project description:Loss of LKB1 leads to aberrant DC maturation and production of cytokines and immunoregulatory molecules. DCs (n = 7 per genotype) were isolated from the spleen, and CD25+CD4+ Tregs (n = 4 for WT, n = 3 for LKB1ΔDC mice) were isolated from the spleen and peripheral lymph nodes of WT and LKB1ΔDC mice.
2019-04-16 | GSE128473 | GEO
Project description:Transcriptional profiling of mouse comparing in vitro-derived DC progenitors from control and Gata2 conditional knockout mice. Two-condition experiment, Control DCs vs. G2 Knockout DCs. Biological replicates: 4 control, 3 Gata2 knockout, independently grown and harvested. One replicate per array. Dendritic cells (DCs) are critical immune response regulators; however, the mechanism of DC differentiation is not fully understood. Heterozygous germline GATA2 mutations induce GATA2 deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia/acute myeloid leukemia, and a profoundly reduced DC population, which is associated with increased susceptibility to viral infections, impaired phagocytosis, and decreased cytokine production. To define the role of GATA2 in DC differentiation and function, we studied Gata2 conditional knockout and haploinsufficient mice. Gata2 conditional deficiency significantly reduced the DC count, whereas Gata2 haploinsufficiency did not affect this population. GATA2 was required for the in vitro generation of DCs from Linâ??Sca-1+Kit+ cells, common myeloid-restricted progenitors, and common dendritic cell precursors, but not common lymphoid-restricted progenitors or granulocyte-macrophage progenitors, suggesting that GATA2 functions in the myeloid pathway of DC differentiation. Moreover, expression profiling demonstrated reduced expression of myeloid-related genes, including mafb, and increased expression of T-lymphocyte-related genes, including Gata3 and Tcf7, in Gata2-deficient DC progenitors. In addition, GATA2 was found to bind an enhancer element 190-kb downstream region of Gata3, and a reporter assay exhibited significantly reduced luciferase activity after adding this enhancer region to the Gata3 promoter, which was recovered by GATA sequence deletion within Gata3 +190. These results suggest that GATA2 plays an important role in cell fate specification toward the myeloid versus T lymphocyte lineage by regulating lineage-specific transcription factors in DC progenitors, thereby contributing to DC differentiation.
2016-05-31 | E-GEOD-82044 | biostudies-arrayexpress
Project description:Transcriptional profiling of mouse comparing in vitro-derived DC progenitors from control and Gata2 conditional knockout mice. Two-condition experiment, Control DCs vs. G2 Knockout DCs. Biological replicates: 4 control, 3 Gata2 knockout, independently grown and harvested. One replicate per array.
2016-05-31 | GSE82044 | GEO
Project description:Cell division cycle 42 (Cdc42) is a member of the Rho GTPase family and has pivotal functions in actin organization, cell migration and proliferation. Cdc42 has been shown to regulate antigen (Ag)-uptake in immature dendritic cells (DC) and controls their migration from tissues to lymph nodes. Previous reports demonstrated that Cdc42 is inactivated upon DC-maturation to avoid continued Ag-acquisition. To further study the molecular mechanisms of DC-control by Cdc42, we used bone marrow-derived DCs from Cdc42-deficient mice. We show that Cdc42-deficient DCs are phenotypically mature without additional maturation stimuli, as they upregulate CD86 from intracellular storages to the cell surface. They also accumulate invariant chain (Ii)-MHC class II complexes at the cell surface, which cannot efficiently present peptide Ag for priming of Ag-specific CD4 T cells. Lack of Cdc42 in immature DCs does not allow MHC class II maturation, as lysosomal Cathepsins are lost into the supernatant and Ii-MHC class II complexes cannot mature. Therefore Cdc42-deficient DCs are "pseudomature" and lose most functional hallmarks of antigen-presenting cells. Our results propose that Cdc42 keeps DCs in an immature state, while downregulation of Cdc42-activity during maturation facilitates generation of CD86+MHCII+ mature DCs.
2015-10-12 | PXD001934 | Pride
Project description:We have described two human, monocyte-derived dendritic cells (DC), which we have termed DC-S (small) and DC-L (large). Human dendritic cells are significantly less well known that murine ones, yet they are a crucial player in the immune system, especially when considering options for immunotherapies. Specifically, monocyte-derived dendritic cells, which are the most amenable for clinically relevant work, are considered by many as only reactive, inflammatory cells. In my work I showed that in fact they consist of two subpopulations, with diverging characteristics: one is steady state-like and more tolerizing in its phenotype (DC-S), and the other is more âdangerousâ, with an inflammatory phenotype (DC-L). This has important implications for the immunobiology of dendritic cells and also for their use in clinical applications.<br> As part of our effort to better characterize them, while immature (day 6 of culture) we sorted them into DC-S and DC-L, replated them with or without LPS for 24 hours, and then extracted the RNA. 3 different experiments were pooled together for the RNA samples. The source of the cells is from random donor blood bank buffy coat preparations - we don't know their identities or demographics. The DCs were prepared as described in our manuscript; briefly, monocytes were isolated from buffy coats using CD14 magnetic beads and cultured for 6 days with 1% autologous plasma, IL4 and GCSF. At day 6 we sorted them as described above.
2016-10-17 | E-MTAB-5075 | biostudies-arrayexpress
Project description:The functional diversification of dendritic cells (DCs) is a key step in establishing protective immune responses. Despite the importance of this lineage diversity, its genetic basis is not fully understood. DC-SCRIPT (Zfp366) is a poorly known transcription factor expressed in conventional DCs (cDCs) and their committed bone marrow progenitors but not in plasmacytoid DCs (pDCs). We show that mice lacking DC-SCRIPT displayed substantially impaired development of IRF8-dependent conventional DC1 (cDC1), while cDC2 differentiated normally. The residual DC-SCRIPT-deficient cDC1s had impaired CD8+ T-cell cross-priming, which could be in part explained by the direct control of DC-SCRIPT on IL-12p40 production. Genome-wide mapping of DC-SCRIPT binding and gene expression analyses revealed a key role for DC-SCRIPT in maintaining cDC1 identity via the direct regulation of cDC1 signature genes, including Irf8. Our study reveals DC-SCRIPT to be a critical component of the gene regulatory program shaping the functional attributes of cDC1s.
2021-02-24 | GSE165138 | GEO
Project description:We determined the microRNA profile of conventional DCs, plasmacytoid DCs, in vitro derived conventional DCs, and DC precursors in the bone marrow. We then compared conventional DCs to plasmacytoid DCs, conventional DCs and in vitro conventional DCs. In addition, we used MDS analysis to compare all the profiles.
2015-05-05 | GSE57442 | GEO