Transcriptional profiling of cDC2 subsets in IFNAR∆CD11c mice treated with allergens
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE276029 | GEO | 2025/07/21
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptional profiling of cDC2 subsets in IFNAR∆CD11c mice treated with allergens
| PRJNA1154305 | ENA
Project description:Purpose: While type I interferons (IFN) are important for control of viral replication, we see that, upon infection of Ifnar-/- females were crossed to Ifnar+/- males with ZIKV, only Ifnar+/- fetuses are resorbed or develop severe growth restriction. To identify how IFN may be altering placenta development, we performed RNAsequencing on infected and uninfected Ifnar-/- and Ifnar+/- placentas. Methods: Ifnar-/- females were crossed to Ifnar+/- males and infected intravaginally with Cambodian ZIKV at E5.5. Placentas were harvested from infected and uninfected pregnant dams at E10.5. Results/ Conclusions: Comparison of ZIKV-infected Ifnar-/- and Ifnar+/- shows an elevated interferon stimulated gene (ISG) signature in Ifnar+/- placentas but does not reveal any underlying developmental defects that may be causing defects in placenta development.
2017-12-31 | GSE98423 | GEO
Project description:Lung-resident conventional dendritic cells (cDCs) coordinate immune responses to respiratory viruses in the respiratory tract or after migration to mediastinal lymph nodes (mLN). Migratory DCs include cDC1s (CD103+XCR1+CD24hi) expressing IRF8 or cDC2s (CD11b+SIRPa+CD24+) expressing IRF4. IRF4+ cDC2s are divided into a CD24hi subset that requires IRF4 for differentiation and a CD24int subset that is present in the absence of IRF4. During influenza A virus (IAV) infection of mice, we characterized the kinetics of cDC2 subset accumulation in the lung and mLN and their differences in IRF4-dependent gene expression and function. We found that the two IRF4-expressing cDC2 subsets upregulated CD86 to high levels, produced IL-12p40 and the chemokines CCL17 and CCL2, and were capable of acquiring antigen in vivo and activating antigen-specific CD8+ T cells. Notably, the CD11b+CD24int cDC2 subset expressed canonical cDC markers and transcription factors and expanded to high numbers in the lung and mLN by day 6 post-infection. Transcriptome analyses on day 5 post-infection revealed that the CD11b+CD24int cDC2 subset expressed both IRF4 and IRF8 and harbored an elevated interferon response signature compared to the CD11b+CD24hi subset. Analyses of mice lacking Irf4 in CD11c+ cells showed that IRF4 promoted the function of CD11b+CD24int cDC2s, including the capacity to migrate to mLN and to produce CCL17 and CCL22, consistent with their altered gene expression profile in the absence of IRF4. In sum, our data show that the two lung-resident CD11b+ cDC2 subsets present in naïve mice elaborated distinct and common functional responses regulated by IRF4 during IAV infection.
2025-01-31 | GSE285970 | GEO
Project description:The transcriptomes of primary isolated unstimulated murine splenic cDC1 and cDC2 from specific pathogen free (SPF) were compared to cDC1 and cDC2 from Germ Free (GF) and Interferon alpha/beta receptor 1 (Ifnar) knock out mice. Total RNA was prepared from sort-purified cDC1 and cDC2 (for each sample 3 individual mice were pooled) using Trizol reagent (Invitrogen) in combination with the miRNeasy Micro Kit (Qiagen) according to the manufacturer’s instructions. For poly-A-dependent cDNA synthesis and a first amplification step 10 ng of total RNA was used as input in the Smart-Seq v4 mRNA Ultra Low Input RNA Kit (Clontech) and processed according to the manufacturer’s instructions. 1 ng of the purified cDNA was used for tagmentation and library completion with the Nextera XT library preparation kit (Illumina). In the following, 2x75nt paired-end sequencing was performed on a NextSeq 500.
2020-03-30 | E-MTAB-8883 | biostudies-arrayexpress
Project description:The divergence of the common dendritic cell progenitor (CDP) into specified progenitors for the cDC1 and cDC2 dendritic cells subsets is poorly understood. Some transcription factors (TFs) act in commitment of already specified progenitors, such as Batf3 which stabilizes Irf8 autoactivation at the +32 kb Irf8 enhancer, but the mechanism of CDP divergence remains unknown. Here, we report the transcriptional basis of CDP divergence and describe the first requirements for pre-cDC2 specification. Genetic epistasis analysis suggested that Nfil3 acts upstream of Id2, Batf3, and Zeb2 in cDC1 development but has not revealed its mechanism or targets. Analysis of newly generated NFIL3 reporter mice showed extremely transient NFIL3 expression during cDC1 specification. CUT&RUN and ChIP-seq analysis identified endogenous NFIL3 binding in the –165 kb Zeb2 enhancer at three sites that also bind CCAAT-enhancer-binding proteins C/EBPa and C/EBPb. In vivo mutational analysis using CRISPR/Cas9 targeting showed that these NFIL3/C/EBP sites are functionally redundant, with C/EBPs supporting and NFIL3 repressing Zeb2 expression at these sites, respectively. Mutation of all three NFIL3/C/EBP sites ablated Zeb2 expression in myeloid, but not lymphoid progenitors, causing complete loss of pre-cDC2 specification and mature cDC2 development in vivo. These mice failed to generate TH2 responses against H. polygyrus infection, consistent with cDC2 supporting TH2 responses to helminths. Thus, CDP divergence is controlled by competition between NFIL3 and C/EBPs at the –165 kb Zeb2 enhancer.
2022-04-19 | GSE188564 | GEO
Project description:The divergence of the common dendritic cell progenitor (CDP) into specified progenitors for the cDC1 and cDC2 dendritic cells subsets is poorly understood. Some transcription factors (TFs) act in commitment of already specified progenitors, such as Batf3 which stabilizes Irf8 autoactivation at the +32 kb Irf8 enhancer, but the mechanism of CDP divergence remains unknown. Here, we report the transcriptional basis of CDP divergence and describe the first requirements for pre-cDC2 specification. Genetic epistasis analysis suggested that Nfil3 acts upstream of Id2, Batf3, and Zeb2 in cDC1 development but has not revealed its mechanism or targets. Analysis of newly generated NFIL3 reporter mice showed extremely transient NFIL3 expression during cDC1 specification. CUT&RUN and ChIP-seq analysis identified endogenous NFIL3 binding in the –165 kb Zeb2 enhancer at three sites that also bind CCAAT-enhancer-binding proteins C/EBPa and C/EBPb. In vivo mutational analysis using CRISPR/Cas9 targeting showed that these NFIL3/C/EBP sites are functionally redundant, with C/EBPs supporting and NFIL3 repressing Zeb2 expression at these sites, respectively. Mutation of all three NFIL3/C/EBP sites ablated Zeb2 expression in myeloid, but not lymphoid progenitors, causing complete loss of pre-cDC2 specification and mature cDC2 development in vivo. These mice failed to generate TH2 responses against H. polygyrus infection, consistent with cDC2 supporting TH2 responses to helminths. Thus, CDP divergence is controlled by competition between NFIL3 and C/EBPs at the –165 kb Zeb2 enhancer.
2022-04-19 | GSE174108 | GEO
Project description:The divergence of the common dendritic cell progenitor (CDP) into specified progenitors for the cDC1 and cDC2 dendritic cells subsets is poorly understood. Some transcription factors (TFs) act in commitment of already specified progenitors, such as Batf3 which stabilizes Irf8 autoactivation at the +32 kb Irf8 enhancer, but the mechanism of CDP divergence remains unknown. Here, we report the transcriptional basis of CDP divergence and describe the first requirements for pre-cDC2 specification. Genetic epistasis analysis suggested that Nfil3 acts upstream of Id2, Batf3, and Zeb2 in cDC1 development but has not revealed its mechanism or targets. Analysis of newly generated NFIL3 reporter mice showed extremely transient NFIL3 expression during cDC1 specification. CUT&RUN and ChIP-seq analysis identified endogenous NFIL3 binding in the –165 kb Zeb2 enhancer at three sites that also bind CCAAT-enhancer-binding proteins C/EBPa and C/EBPb. In vivo mutational analysis using CRISPR/Cas9 targeting showed that these NFIL3/C/EBP sites are functionally redundant, with C/EBPs supporting and NFIL3 repressing Zeb2 expression at these sites, respectively. Mutation of all three NFIL3/C/EBP sites ablated Zeb2 expression in myeloid, but not lymphoid progenitors, causing complete loss of pre-cDC2 specification and mature cDC2 development in vivo. These mice failed to generate TH2 responses against H. polygyrus infection, consistent with cDC2 supporting TH2 responses to helminths. Thus, CDP divergence is controlled by competition between NFIL3 and C/EBPs at the –165 kb Zeb2 enhancer.
2022-04-19 | GSE188482 | GEO
Project description:Distinct subsets of circulating human cDC2 dendritic cells were sorted based on CD5, CD163 and CD14 expression, including a subset of inflammatory CD5-CD163+CD14+ cells related to DC3s which were expanded in systemic lupus eryhtematosus (SLE) patients and correlated with disease activity.
2019-09-02 | GSE136731 | GEO
Project description:Type 2 pre-cDCs are considered as a homogeneous population in the bone marrow but have show that this is not the case in mice. We used single cell RNA sequencing to show that the bone marrow of humas, as it is the case for mice, contains two subsets of progenitors that are primed to give rise to different cDC2 subsets in peripheral tissues.
2024-02-26 | GSE244346 | GEO
Project description:Atopic and allergic diseases predominantly manifest in early life, a period of profound growth and maturation. Yet, there is a dearth of information on the impact of developmental parameters on the neonatal immune reaction to allergens. Here we demonstrate that common allergens including house dust mite (HDM) elicited potent type 17 inflammatory responses from neonatal but not adult mice. HDM-induced inflammation was abolished in Rorgt-, gd T cell-, or epithelial IL-17RC- deficient animals and surprisingly did not require nociceptors or lymph node engagement. Instead, neonatal CD301b+ type 2 conventional dendritic cells (cDC2s) abundantly engulfed allergen and locally activated gd T cells in the skin. Despite uptaking equivalent antigen to neonates, adult cDC2s did not promiscuously activate in the skin. Mechanistically, this discrepancy was not attributable to cell-intrinsic differences arising from the distinct developmental origins of neonatal and adult cDC2s. Instead, neonatal cDC2 hyperactivation could be traced to a lower systemic glucocorticoid level, a consequence of an immature hypothalamic-pituitary-adrenal (HPA) axis in early life, and could be reversed by cortisol administration at the time of allergen challenge. These findings bring to fore the influence of organismal developmental factors in shaping immune sensitivity to allergens in early life.
2025-06-17 | GSE299934 | GEO