The affect of specific ablation of Runx3 from Esam splenic dendritic cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE48590 | GEO | 2014/06/22
SECONDARY ACCESSION(S): PRJNA210762
REPOSITORIES: GEO
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Project description:Esam/CD4+ dendritic cells are part of the innate immunity essential for priming and activating of CD4+ T cells To identify Runx3 responsive genes Esam dendritic cells were freshly sorted from macs enriched splenic DCs taken from 6 weeks old mice. Four samples from four mice were sorted and analyzed where in each littermates pair consisted of a control and Runx3 conditional KO. Mice lacking Runx3 specifically in the DC compartment were produced by crossing Runx3fl/fl mice onto CD11c-Cre mice. This mating scheme generated Runx3fl/fl/CD11c:Cre (CD11c-DC-Runx3Δ) mice.
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Project description:CD4+ dendritic cells are part of the innate immunity essential for priming and activating of CD4+ T cells
2014-06-22 | GSE48589 | GEO
Project description:CD4+ dendritic cells are part of the innate immunity essential for priming and activating of CD4+ T cells To identify Runx3 responsive genes CD4+ dendritic cells were sorted from freshly isolated macs enriched splenic DCs taken from 6 weeks old mice. Six samples from six mice were sorted and analyzed where in each littermates pair consisted of a control and Runx3 KO.
2014-06-22 | E-GEOD-48589 | biostudies-arrayexpress
Project description:Defense against attaching and effacing (A/E) bacteria requires the sequential generation of IL-23 and IL-22 to induce protective mucosal responses. While the critical source of IL-22 has been identified as CD4+ and Nkp46+ innate lymphoid cells (ILCs), the precise source of IL-23 is unclear. Here, we use genetic techniques to deplete specific classical dendritic cell (cDC) subsets and analyze immunity to the A/E pathogen Citrobacter rodentium. We find that Zbtb46+ cDCs, and specifically Notch2-dependent intestinal CD11b+ cDCs, but not Batf3-dependent CD103+ cDCs, are required for IL-23 production and immunity against C. rodentium. Notch2 controls cDC differentiation at a terminal step mediated by lymphotoxin signaling. Importantly, these results provide the first demonstration of a non-redundant function of CD11b+ cDCs in vivo. Analysis of differentially expressed genes in ESAM+ and ESAM- CD11b+ and DEC205+ splenic classical DC subsets. Splenocytes were harvested from WT C57Bl/6 or WT Cx3cr1-gfp mice and cDC subsets sorted to >95% purity on the FACSAriaII.
2013-06-01 | E-GEOD-45679 | biostudies-arrayexpress
Project description:Dendritic cells (DCs) in tissues and lymphoid organs comprise distinct functional subsets that differentiate in situ from circulating progenitors. Tissue-specific signals that regulate DC subset differentiation are poorly understood. We report that DC-specific deletion of the Notch2 receptor caused a reduction of DC populations in the spleen. Within the splenic CD11b+ DCs, Notch signaling blockade ablated a distinct population marked by high expression of adhesion molecule Esam. The Notch-dependent Esamhi DC subset also required lymphotoxin beta receptor signaling, proliferated in situ and facilitated efficient CD4+ T cell priming. The Notch-independent Esamlo DCs expressed monocyte-related genes and showed superior cytokine responses. In addition, Notch2 deletion led to the loss of CD11b+ CD103+ DCs in the intestinal lamina propria and to the corresponding decrease of IL-17-producing CD4+ T cells in the intestine. Thus,Notch2 is a common differentiation signal for T cell-priming CD11b+ DC subsets in the spleen and intestine. We compared genome-wide expression profiles of wild-type Esam(hi) and Esam(lo) splenic CD11b+ DC populations, along with CD11b+ DCs from DC-RBPJΔ mice. Spleens from 2-3 Cx3cr1-GFP+ RBPJflox/flox CD11c-Cre+ mice or Cx3cr1-GFP+ RBPJflox/flox Cre-negative littermate controls were isolated, pooled and depleted of lymphoid and erythroid cells by negative selection on MACS columns. Live cells were stained for surface expression of CD11c, CD11b and Esam. CD11c(hi) CD11b+ DCs from control mice could be separated into Esam(lo) GFP(hi) versus Esam(hi) GFP(lo) subsets. CD11c(hi) CD11b+ DCs from RBPJ-targeted mice spleens were uniformly Esam(lo) GFP(hi). The two subsets from control mice and single Esam(lo) GFP(hi) subset from RBPJ-targeted mice were sorted using FACSAria II flow sorter and analyzed using GeneChip Mouse Gene 1.0 ST Array (Affymetrix).
2011-10-31 | E-GEOD-31551 | biostudies-arrayexpress
Project description:Runx3 regulated genes in splenic CD4+ dendritic cells
| PRJNA210761 | ENA
Project description:Dendritic cells (DCs) in tissues and lymphoid organs comprise distinct functional subsets that differentiate in situ from circulating progenitors. Tissue-specific signals that regulate DC subset differentiation are poorly understood. We report that DC-specific deletion of the Notch2 receptor caused a reduction of DC populations in the spleen. Within the splenic CD11b+ DCs, Notch signaling blockade ablated a distinct population marked by high expression of adhesion molecule Esam. The Notch-dependent Esamhi DC subset also required lymphotoxin beta receptor signaling, proliferated in situ and facilitated efficient CD4+ T cell priming. The Notch-independent Esamlo DCs expressed monocyte-related genes and showed superior cytokine responses. In addition, Notch2 deletion led to the loss of CD11b+ CD103+ DCs in the intestinal lamina propria and to the corresponding decrease of IL-17-producing CD4+ T cells in the intestine. Thus,Notch2 is a common differentiation signal for T cell-priming CD11b+ DC subsets in the spleen and intestine.
2011-10-31 | GSE31551 | GEO
Project description:Classical dendritic cells (cDC) are specialized antigen-presenting cells mediating immunity and tolerance. cDC cell-lineage decisions are largely controlled by transcriptional factor regulatory cascades. Using an in vivo cell-specific targeting of Runx3 at various stages of DC lineage development we show that Runx3 is required for cell-identity, homeostasis and function of splenic Esam(hi) DC. Ablation of Runx3 in DC progenitors led to a substantial decrease in splenic CD4(+)/CD11b(+) DC. Combined chromatin immunoprecipitation sequencing and gene expression analysis of purified DC-subsets revealed that Runx3 is a key gene expression regulator that facilitates specification and homeostasis of CD11b(+)Esam(hi) DC. Mechanistically, loss of Runx3 alters Esam(hi) DC gene expression to a signature characteristic of WT Esam(low) DC. This transcriptional reprogramming caused a cellular change that diminished phagocytosis and hampered Runx3(-/-) Esam(hi) DC capacity to prime CD4(+) T cells, attesting to the significant role of Runx3 in specifying Esam(hi) DC identity and function.
| S-EPMC3817345 | biostudies-literature
Project description:ChIP-seq was conducted using FACS-isolated CD11chiMHCII+CD4+ splenic WT DC and anti-Runx3 antibodies (Ab). Two biological Runx3 IP repeats and two input controls from sorted CD4 DC
2014-06-22 | E-GEOD-48588 | biostudies-arrayexpress