Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection (microarray)

ABSTRACT: The phenotypic and functional dichotomy between IRF8+ type 1 and IRF4+ type 2 conventional dendritic cells (cDC1-cDC2) is well accepted; it is unknown how robust this dichotomy is under inflammatory conditions, when additionally monocyte-derived cells (MCs) become competent antigen presenting cells (APC). Using single-cell technologies in models of respiratory viral infection, we found that lung cDC2s acquired expression of Fc receptor CD64 shared with MCs, and of IRF8 shared with cDC1s. These inflammatory (Inf-)cDC2s were superior in inducing CD4+ T helper (Th) cell polarization while simultaneously presenting antigen to CD8+ T cells. When carefully separated from inf-cDC2s, MCs lacked APC function. Inf-cDC2 matured in response to cell-intrinsic toll-like receptor and type 1 interferon receptor signaling, upregulated an IRF8-dependent maturation module and acquired antigens via convalescent serum and Fc receptors. Since hybrid inf-cDC2s are easily confused with monocyte-derived cells, their existence could explain why APC functions have been attributed to MCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE149618 | GEO | 2020/05/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection (scRNA-Seq)

Project description:The phenotypic and functional dichotomy between IRF8+ type 1 and IRF4+ type 2 conventional dendritic cells (cDC1-cDC2) is well accepted; it is unknown how robust this dichotomy is under inflammatory conditions, when additionally monocyte-derived cells (MCs) become competent antigen presenting cells (APC). Using single-cell technologies in models of respiratory viral infection, we found that lung cDC2s acquired expression of Fc receptor CD64 shared with MCs, and of IRF8 shared with cDC1s. These inflammatory (Inf-)cDC2s were superior in inducing CD4+ T helper (Th) cell polarization while simultaneously presenting antigen to CD8+ T cells. When carefully separated from inf-cDC2s, MCs lacked APC function. Inf-cDC2 matured in response to cell-intrinsic toll-like receptor and type 1 interferon receptor signaling, upregulated an IRF8-dependent maturation module and acquired antigens via convalescent serum and Fc receptors. Since hybrid inf-cDC2s are easily confused with monocyte-derived cells, their existence could explain why APC functions have been attributed to MCs.

2020-05-08 | GSE149617 | GEO

Myocardial infarction (MI) primes autoreactive T cells through activation of dendritic cells

Project description:DC subsets of the murine healthy heart consisted of IRF8-dependent conventional (c)DC1, IRF4-dependent cDC2 and monocyte-derived DCs. In steady state, cardiac self-antigen α-myosin was presented in heart-draining mediastinal lymph node (mLN) by cDC1s, driving the proliferation of antigen-specific CD4+ TCR-M T cells, and their differentiation into Tregs. Following MI, all DC subsets infiltrated the heart, while only cDCs migrated to the mLN. Here, cDC2s induced TCR-M proliferation and differentiation into IL-17/IFNγ producing effector cells. Thus, cardiac specific autoreactive T cells get activated by mature DCs following myocardial infarction.

2017-03-15 | GSE94949 | GEO

The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2

Project description:Plasmacytoid dendritic cells (pDCs) develop from pre-pDCs, while two lineages of conventional DCs (cDC1s and cDC2s) develop from lineage-committed pre-cDCs. A number of transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2, Id2) and cDC1s (IRF8, Id2 and Batf3) however, those required for the early commitment of pre-cDCs towards the cDC2 lineage are unknown. Here we identified the TF Zinc finger E box binding homeobox 2 (Zeb2), to play a crucial role in regulating DC development. Zeb2 was expressed from the pre-pDC and pre-cDC stage onwards, and highly expressed in mature pDCs and cDC2s. Mice conditionally lacking Zeb2 in CD11c+ cells had a cell intrinsic reduction in pDCs and cDC2s, coupled with an increase in cDC1s. Conversely, mice in which CD11c+ cells overexpressed Zeb2 displayed a reduction in cDC1s. This was accompanied by altered expression of Id2, which was upregulated in cDC2s and pDCs from conditional knock-out mice. Zeb2 ChIP analysis revealed Id2 to be a direct target of Zeb2. Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC lineages through repression of Id2.

2016-05-01 | GSE79903 | GEO

Human blood CD1c⁺ dendritic cells encompass CD5-high and CD5-low subsets that differ significantly in phenotype, gene expression and functions

Project description:There are three major dendritic cell (DC) subsets in both human and mouse, plasmacytoid DCs (pDCs) and two types of conventional DCs (cDCs), cDC1s and cDC2s. cDC2s are important for polarizing CD4+ naive T cells into different subsets including Th1, Th2, Th17, Th22 and regulatory T cells (Tregs). In mice, cDC2s can be further divided into phenotypically and functionally distinct subgroups. However, subsets of human cDC2s have not been reported. In the present study, we showed that human blood CD1c+ conventional DCs (cDC2s) can be further separated into two subpopulations according to their CD5 expression status. Comparative transcriptome analyses showed that the CD5high DCs expressed higher levels of cDC2-specific genes, including IRF4, which is essential for the cDC2 development and its migration to lymph nodes. In contrast, CD5low DCs preferentially expressed monocyte-related genes, including the lineage-specific transcription factor MAFB. Furthermore, compared with CD5low subpopulation, CD5high subpopulation showed stronger migration toward CCL21 and overrepresentation among migratory DCs in lymph nodes. Additionally, the CD5high DCs induced naïve T-cell proliferation more potently than the CD5low DCs. Moreover, CD5high DCs induced higher levels of IL-10-, IL-22- and IL-4-producing T-cell formation, whereas CD5low DCs induced higher levels of IFN-γ-producing T-cell formation. Thus, we show that human blood CD1c+ cDC2s encompass two subsets that differ significantly in phenotype, gene expression, and functions. We propose that these two subsets of human cDC2s could potentially play contrasting roles in immunity or tolerance.

2017-03-07 | GSE77649 | GEO

Ablation of Adar1 in myeloid cells imprints a global antiviral state in the lung and heightens early immunity against SARS-CoV-2 [scRNA-Seq]

Project description:Under normal homeostatic conditions, self double-stranded RNA (self-dsRNA) is modified by adenosine deaminase acting on RNA 1 (ADAR1) to prevent the induction of a type I interferon (IFN) mediated inflammatory cascade. Antigen presenting cells (APCs) sense pathogen associated molecular patterns (PAMPs), such as dsRNA, to activate the immune response. The impact of ADAR1 on the function of APCs and the consequences on immunity is poorly understood. Here, we show that ADAR1 deletion in CD11c+ APCs leads to: (i) a skewed myeloid cell compartment enriched in inflammatory cDC2s (inf-cDC2) like cells; (ii) enhanced numbers of activated tissue resident memory T cells (TRMs) in the lung; and (iii) the imprinting of a broad antiviral transcriptional signature across both immune and non-immune cells. Further the resulting changes can be partially reversed by blocking IFNAR1 signaling and promote early resistance against SARS-CoV-2 infection. Our study provides insight into the consequences of self-dsRNA sensing in APCs on the immune system in the context of viral challenge.

2023-01-22 | GSE222487 | GEO

Ablation of Adar1 in myeloid cells imprints a global antiviral state in the lung and heightens early immunity against SARS-CoV-2 [RNA-Seq]

2023-01-22 | GSE222326 | GEO

Irf8 deficiency induces functional, transcriptional and epigenetic reprogramming of cDC1 into the cDC2 lineage

Project description:Conventional dendritic cells (cDC) consist of two functionally and phenotypically distinct subsets, cDC1 and cDC2, whose development is dependent on distinct sets of transcription factors. Interferon regulatory factor 8 (IRF8) is required at multiple stages of cDC1 development, but its role in mature cDC1 remains unclear. Here we used XCR1-cre to delete Irf8 in committed cDC1 and demonstrate that Irf8 is required for maintaining the identify of cDC1 but not their survival. In the absence of Irf8, committed cDC1 (“ex-cDC1”) acquired the transcriptional, functional and chromatin accessibility properties of cDC2. This conversion was independent on Irf4 and was associated with decreased accessibility in putative IRF8, Batf3 and composite AP-1-IRF (AICE) binding elements, together with increased accessibility of cDC2 associated transcription factor binding elements. Thus, IRF8 expression by committed cDC1 is required for preventing their conversion into cDC2.

2022-06-21 | GSE168477 | GEO

Single-cell transcriptomic analysis of mouse lung cDC2s at various times post allergic sensitization

Project description:Conventionaldendritic cells (cDCs) in the lung that drive effector T cell differentiation, and initiate allergic responses upon inhalation of allergens. CD11b+type 2 cDCs (cDC2s) are heterogeneous, but the relationship among subpopulations has been elusive. To analyze their developmental pathways of cDC2 subpopulations, we performed single cell RNA-sequencing (scRNAS-Seq) of total lung cDC2s at various times following inhalation of house dust extracts, and detected multiple clusters based on their differential transcriptomes. The data of cDC2 transcriptome at steady state, early and later stages after activation will be applicable for the maturation pathway analysis of cDC2s.

2024-06-05 | GSE261034 | GEO

Optimization of the Irf8 +32 kb enhancer disrupts dendritic cell lineage segregation [scRNA-seq]

Project description:Autoactivation of lineage-determining transcription factors (TFs) mediates bistable expression to generate distinct cell phenotypes essential for complex body plans. Classical dendritic cells type 1 (cDC1) and type 2 (cDC2) provide non-redundant functions required for defense against distinct immune challenges. Interferon Regulatory Factor 8 (IRF8), the cDC1 lineage-determining TF, undergoes autoactivation in cDC1 progenitors to establish cDC1 identity, yet its expression is downregulated during cDC2 differentiation by an unknown mechanism. This study reveals that the Irf8 +32 kb enhancer, responsible for IRF8 autoactivation, has been tuned to possess low-affinity IRF8 binding sites. Incorporation of multiple high-affinity IRF8 binding sites into the Irf8 +32 kb enhancer induces erroneous IRF8 autoactivation in specified cDC2 progenitors, causing their redirection towards cDC1 and a novel hybrid DC subset with mixed lineage phenotypes. These developmental alterations critically impair both cDC1- and cDC2-dependent arms of immunity. Collectively, our findings underscore the significance of enhancer suboptimization in the developmental segregation of classical dendritic cells required for normal immune function.

2024-08-18 | GSE270060 | GEO

Classical dendritic cells are required for dietary antigen-mediated peripheral regulatory T cell and tolerance induction I

Project description:Oral tolerance prevents pathological inflammatory responses towards innocuous foreign antigens via peripheral regulatory T cells (pTreg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure to instruct naÃ¯ve CD4+ T cells to differentiate into pTreg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs are dispensable, while classical dendritic cells (cDCs) are critical for pTreg cell induction and oral tolerance. CD11bÂ¬â cDCs from the gut-draining lymph nodes efficiently induced pTreg cells, and conversely, loss of IRF8-dependent CD11bâ cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in pTreg cell induction and their redundancy during oral tolerance development. Four dendritic cell subpopulations from mouse mesenteric lymphnodes were sorted and compared in their gene expression profile

2016-03-28 | E-GEOD-77303 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data