Microarray analysis of WT and Batf3-/- CD8alpha dendritic cells from C57BL/6 spleen
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE40647 | GEO | 2012/09/30
SECONDARY ACCESSION(S): PRJNA174468
REPOSITORIES: GEO
Similar Datasets
Project description:Batf3 regulates key CD8alpha DC-specific genes. WT and KO cells were isolated from pooled spleens of C57BL/6 genetic background mice, that were either untreated, or injected with recombinant murine IL-12 in pyrogen-free saline at 2.5 ug/mL. Mice were injected i.p. with 0.5 ug of IL-12 once and sorted after 3 days. CD8alpha+ dendritic cells were sorted as B220- NK1.1- CD172a- CD11c+ MHCII+ CD24+ DEC205+ CD8alpha+ cells.
2012-09-30 | E-GEOD-40647 | biostudies-arrayexpress
Project description:The transcription factors Batf3 and IRF8 are required for development of CD8α+ conventional dendritic cells (cDCs), but the basis for their actions was unclear. Here, we identify two novel Zbtb46+ progenitors that separately generate CD8α+ and CD4+ cDCs and arise directly from the common DC progenitor (CDP). Irf8 expression in the CDP depends on prior PU.1-dependent autoactivation, and specification of pre-CD8 DC progenitors requires IRF8 but not Batf3. However, upon pre-CD8 DC specification, Irf8 autoactivation becomes Batf3-dependent at a CD8α+ cDC-specific enhancer containing multiple AP1-IRF composite elements (AICEs) within the Irf8 superenhancer. CDPs from Batf3-/- mice that specify toward pre-CD8 DCs fail to complete CD8α+ cDC development due to decay of Irf8 autoactivation, and divert to the CD4+ cDC lineage. Examination of histone modifications (H3K27ac and H3K4me1) and 2 transcription factors (Batf3 and Irf8) and the p300 co-factor binding in 3 different dendritic cell subsets
2015-06-08 | E-GEOD-66899 | biostudies-arrayexpress
Project description:The transcription factors Batf3 and IRF8 are required for development of CD8α+ conventional dendritic cells (cDCs), but the basis for their actions was unclear. Here, we identify two novel Zbtb46+ progenitors that separately generate CD8α+ and CD4+ cDCs and arise directly from the common DC progenitor (CDP). Irf8 expression in the CDP depends on prior PU.1-dependent autoactivation, and specification of pre-CD8 DC progenitors requires IRF8 but not Batf3. However, upon pre-CD8 DC specification, Irf8 autoactivation becomes Batf3-dependent at a CD8α+ cDC-specific enhancer containing multiple AP1-IRF composite elements (AICEs) within the Irf8 superenhancer. CDPs from Batf3-/- mice that specify toward pre-CD8 DCs fail to complete CD8α+ cDC development due to decay of Irf8 autoactivation, and divert to the CD4+ cDC lineage.
2015-06-08 | GSE66899 | GEO
Project description:Anti-viral CD8 T cell responses are characterized by an initial activation/priming of T lymphocytes followed by a massive proliferation, subset differentiation, population contraction and the development of a stable memory pool. The transcription factor BATF3 has been shown to play a central role in the development of conventional dendritic cells (cDC1), which in turn are critical for the optimal priming of CD8 T cells. Here we show that BATF3 is expressed within the first days after priming but has long-lasting T cell intrinsic effects. We found that T cells that lack Batf3 show a normal expansion and differentiation, yet succumbed to an aggravated contraction and had a diminished memory response. Vice versa BATF3-overexpression in CD8 T cells promoted their survival and transition to memory. Mechanistically, BATF3 regulates T cell apoptosis and longevity via the proapoptotic factor BIM. By programing CD8 T cell survival and memory, BATF3 is a promising molecule to optimize adoptive T cell therapy in patients.
2020-08-31 | GSE143504 | GEO
Project description:Anti-viral CD8 T cell responses are characterized by an initial activation/priming of T lymphocytes followed by a massive proliferation, subset differentiation, population contraction and the development of a stable memory pool. The transcription factor BATF3 has been shown to play a central role in the development of conventional dendritic cells (cDC1), which in turn are critical for the optimal priming of CD8 T cells. Here we show that BATF3 is expressed within the first days after priming but has long-lasting T cell intrinsic effects. We found that T cells that lack Batf3 show a normal expansion and differentiation, yet succumbed to an aggravated contraction and had a diminished memory response. Vice versa BATF3-overexpression in CD8 T cells promoted their survival and transition to memory. Mechanistically, BATF3 regulates T cell apoptosis and longevity via the proapoptotic factor BIM. By programing CD8 T cell survival and memory, BATF3 is a promising molecule to optimize adoptive T cell therapy in patients.
2020-08-31 | GSE153341 | GEO
Project description:Batf3-/- mice have impaired development of DC1 . However, DC1 development is restored in Batf3-/- mice containing an Irf8VENUS transgene. Even though DC1 development was restored in these mice, they were still unable to reject a transplanted immunogenic fibrosarcoma, indicating that there are some functions of Batf3-dependent dendritic cells that are not restored by the Irf8VENUS transgene.
2018-11-30 | GSE111034 | GEO
Project description: Not available
| S-BSST950 | biostudies-other
Project description:Conventional dendritic cells (cDCs) are traditionally subdivided into cDC1 and cDC2 lineages. Batf3 is a cDC1-required transcription factor, and we observed that Batf3-/- mice harbor a population of cDC1-like cells co-expressing cDC2-associated surface molecules. Using single cell RNA sequencing with integrated cell surface protein expression (CITE-seq), we found that Batf3-/- mitotic immature cDC1-like cells showed reduced expression of cDC1 features and increased levels of cDC2 features. In wildtype, we also observed a proportion of mature cDC1 cells expressing surface features characteristic to cDC2, and found that overall cDC cell state heterogeneity was mainly driven by developmental stage, proliferation and maturity. We detected population diversity within Sirpa+ cDC2 cells, including a Cd33+ cell state expressing high levels of Sox4 and lineage-mixed features characteristic to cDC1, cDC2, pDCs and monocytes. In conclusion, these data suggest that multiple cDC cell states can co-express lineage-overlapping features, revealing a level of previously unappreciated cDC plasticity.
2021-02-24 | GSE149544 | GEO
Project description:BATF3 has been shown to inhibit FOXP3 expression in differentiating CD4 T cells, however, the role of IRF4 in this inhibition is unexplored. IRF4 binds DNA weakly on its own and requires interactions with other transcription factors. We investigated how BATF3/IRF4 interactions are necessary for IRF4 binding and BATF3-mediated FOXP3 inhibition.
2022-08-16 | GSE211182 | GEO
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 Notch2-dependent genes in CD11b+ and DEC205+ splenic classical DC subsets. Splenocytes were harvested from littermate WT Notch2 f/f C57Bl/6 or Notch2 CD11c-cre C57Bl/6 mice and DC subsets sorted to >95% purity on the FACSAriaII.
2013-06-01 | E-GEOD-45681 | biostudies-arrayexpress