Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regulation of gene expression in splenic cDC1 isolated from WT vs XCR1-/- miceNK cells orchestrate cDC1 migration to potentiate antiviral protective CD8+ T cell responses

ABSTRACT: The expression of the XCR1 chemokine receptor univocally identifies all type 1 conventional dendritic cells (cDC1) throughout the body. The gene encoding its ligand, XCL1, is expressed constitutively by innate lymphoid cells such as natural killer (NK) cells. The evolutionary conservation of XCR1, XCL1 in vertebrates suggests that they play a critical, yet uncharacterized, role in immune responses. Here we showed using mouse cytomegalovirus (MCMV) infection, that the XCL1/XCR1 axis promoted the intra-splenic repositioning of cDC1 towards IFN--producing NK cells forming superclusters around infected cells. There, cDC1 and NK cells engaged into physical interactions enhancing their respective production of IL-12 and IFN-. This feed-forward mechanism also led to NK cell production of GM-CSF, which upregulated CCR7 on cDC1, instructing them to migrate into the T cell area for the priming of CD8+ T cells. In conclusion, we identified a novel mechanism through which NK cells boost the relay between innate and adaptive immunities by regulating the spatiotemporal functions of cDC1.

ORGANISM(S): Mus musculus

PROVIDER: GSE142402 | GEO | 2021/09/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

XCR1 expression distinguishes human conventional dendritic cells type 1 with full effector functions from their immediate precursors

Project description:Dendritic cells (DCs) are major regulators of innate and adaptive immune responses. DCs can be classified into plasmacytoid DCs and conventional DCs (cDCs) type 1 and 2. Murine and human cDC1 share the mRNA expression of XCR1. Murine studies indicated a specific role of the XCR1-XCL1 axis in the induction of immune responses. Here, we describe that human cDC1 can be distinguished into XCR1- and XCR1+ cDC1 in lymphoid as well as non-lymphoid tissues. Steady state XCR1+ cDC1 display a pre-activated phenotype compared to XCR1- cDC1. Upon stimulation, XCR1+ cDC1, but not XCR1- cDC1, secreted high levels of inflammatory cytokines as well as chemokines. This was associated with enhanced activation of NK cells mediated by XCR1+ cDC1. Moreover, XCR1+ cDC1 excelled in inhibiting replication of Influenza A virus. Further, under DC differentiation conditions, XCR1- cDC1 developed into XCR1+ cDC1. After acquisition of XCR1 expression, XCR1- cDC1 secreted comparable level of inflammatory cytokines. Thus, XCR1 is a marker of terminally differentiated cDC1 that licenses the antiviral effector functions of human cDC1, while XCR1- cDC1 seem to represent a late immediate precursor of cDC1.

2023-07-31 | GSE237715 | GEO

Comparision of transcriptomes between murine WT type 1 conventional DCs to XCR1-deficient type 1 conventional DCs

Project description:We sought to compare the overall transcriptomic differences between TLR stimulated WT and XCR1-deficient type 1 conventional DCs. In addition, we also wanted to investigate functional role of XCR1 signaling in WT type 1 conventional DCs by treating recombinant murine XCL1, a ligand of XCR1 to these cells as well

2023-06-01 | GSE228392 | GEO

XCR1+ type 1 conventional dendritic cells drive liver pathology in Non-Alcoholic Steatohepatitis [scRNA-seq]

Project description:Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are prevalent liver conditions, which underlie the development of life-threatening cirrhosis, liver failure and liver cancer. Chronic necro-inflammation is a critical factor in development of NASH, yet the cellular and molecular mechanisms of immune dysregulation in this disease are poorly understood. Here, using single cell transcriptomic analysis, we comprehensively profiled the immune composition of the mouse liver during NASH. We identified a significant pathology-associated increase in hepatic conventional dendritic cells (cDC), and further defined their source as NASH-induced boost in cycling of cDC progenitors in the bone marrow. Analysis of blood and liver from patients on the NALFD/NASH spectrum showed that cDC type 1 (cDC1) were more abundant and activated in disease. Genomic analysis of cDC-T pairs in liver draining lymph nodes revealed that cDCs in NASH promote inflammatory T cell reprogramming, previously associated with NASH worsening. Finally, depletion of cDC1 in XCR1DTA mice or using anti-XCL1 blocking antibody attenuated liver pathology in NASH mouse models. Overall, our study provides a comprehensive characterization of cDC biology in NASH, and identifies XCR1+ cDC1 as an important driver of liver pathology.

2021-05-21 | GSE169445 | GEO

XCR1+ type 1 conventional dendritic cells drive liver pathology in Non-Alcoholic Steatohepatitis [10x scRNA-seq]

2021-05-21 | GSE169446 | GEO

XCR1+ Dendritic Cell-Induced CD4+ T Helper-1 Activation Leads to Exacerbation of Remodeling after Myocardial Infarction

Project description:Th1 is the predominant phenotype during the early stage of MI. XCR1+ cDC1 activated CXCR3+ Th1 could be a novel therapeutic target for ischemic cardiac remodeling.

2023-02-06 | GSE195915 | GEO

cDC1 derived IL27 regulates the transcriptional profile of SI-LP Th subsets

Project description:To assess the broader impact of cDC1 derived IL-27 on the properties of SI-LP CD4+ T cells, these cells were sorted from Xcr1-cre.p28fl/fl mice and p28fl/fl controls (4 mice/group) and subjected to single cell RNA sequencing (scRNA-seq).

2022-11-30 | GSE218311 | GEO

XCR1+ Dendritic Cell-Induced CD4+ T Helper-1 Activation Leads to Exacerbation of Remodeling after Myocardial Infarction (T cell research)

Project description:Th1 is the predominant phenotype during the early stage of MI. XCR1+ cDC1 activated CXCR3+ Th1 could be a novel therapeutic target for ischemic cardiac remodeling.

2023-02-06 | GSE195910 | 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

Thymic XCR1+ dendritic cells undergo a functional maturation fundamentally similar to that of peripheral tolerogenic XCR1+ dendritic cells

Project description:Dendritic cells (DC) play critical roles in central and peripheral T cell tolerance. DC found in the steady-state periphery undergo an homeostatic, tolerogenic, maturation that promotes interaction with naive T cells and induction of abortive responses. In contrast, thymic DC are thought to exist solely in an immature state. In this study, we show that XCR1+ thymic DC constitutively mature into a stage characterized by high levels of molecules involved in T cell activation. This unanticipated mature stage corresponded to a third of the XCR1+ thymic DC and fully accounted for their ability to cross-present self-antigens to developing T cells. Transcriptomic analysis of the XCR1+ DC found in thymus and steady-state periphery revealed that their maturation involves profound and convergent changes. Unexpectedly, maturation resulted in down-regulation of genes conferring their specific function on XCR1+ DC. Paradoxically, upon maturation, central and peripheral tolerogenic XCR1+ DC up-regulated many genes thought to drive pro-inflammatory T-cell responses. Thus, our results reveal that thymic XCR1+ DC undergo constitutive maturation and emphasize the common mechanisms operating for both central and peripheral tolerance induction by XCR1+ DC. DC were isolated from lymphoid organs as previously described (Vremec et al., 2000). DC subsets were sorted by flow cytometry according to the marker combinations described in the âcharacteristics: phenotypeâ field for each sample.

2016-08-22 | E-GEOD-71166 | biostudies-arrayexpress

Regulation of gene expression in splenic cDC1 isolated from WT vs XCR1-/- miceNK cells orchestrate cDC1 migration to potentiate antiviral protective CD8+ T cell responses

Project description:Regulation of gene expression in splenic cDC1 isolated from WT vs XCR1-/- miceNK cells orchestrate cDC1 migration to potentiate antiviral protective CD8+ T cell responses

| PRJNA596923 | ENA

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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