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Long noncoding RNA signatures induced by TLR7 and type I IFN signaling in activated human plasmacytoid dendritic cells

ABSTRACT: Long noncoding RNA signatures induced by TLR7 and type I IFN signaling in activated human plasmacytoid dendritic cells

PROVIDER: PRJNA481248 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7524680_1.fastq.gz	Fastqsanger.gz
	SRR7524680_2.fastq.gz	Fastqsanger.gz
	SRR7524681_1.fastq.gz	Fastqsanger.gz
	SRR7524681_2.fastq.gz	Fastqsanger.gz
	SRR7524682_1.fastq.gz	Fastqsanger.gz

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Long noncoding RNA signatures induced by TLR7 and type I IFN signaling in activated human plasmacytoid dendritic cells

Project description:Using genome-wide sequencing approaches we viewed the contributions of Toll-like receptor 7 (TLR7) and type I interferon (IFN-I) in the regulation of coding and noncoding RNA expression in CAL-1 pDC treated with R848 or IFNβ. Functional enrichment analysis revealed both the unique and synergistic roles of TLR7 and IFN-I signaling in the orchestration of pDC function.

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Reduction of TLR7/8-Induced IFN-I Responses by Plasmacytoid Dendritic Cells in a Longitudinal Cohort of Trans Men

Project description:Type I interferons (IFN-I) are important mediators of antiviral immunity and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females exert an elevated capacity to produce IFN-I in response to activation of toll-like receptor 7 (TLR7) compared to male pDCs, and both hormones and genes encoded by the X chromosome have been implicated in these sex-specific differences. Using longitudinal samples collected from a cohort of trans men receiving testosterone injections as gender-affirming hormone therapy (GAHT), the impact of testosterone on TLR7-mediated IFN-I production by pDCs was assessed. GAHT induced testosterone and estradiol levels within male reference ranges and increased hemoglobin and hematocrit levels, demonstrating biological activity of testosterone. scRNA seq of pDCs showed downregulation of IFN-I-related gene expression signatures, but also revealed inter-donor heterogeneity on the transcriptional level. Longitudinal quantification of IFN-I protein production by pDCs following TLR7-stimulation showed significant and continuous reduction of IFN-I production in trans men, and reduced expression of IFN-I-stimulated genes. These longitudinal studies in trans men demonstrate that testosterone can reduce IFN-I production by pDCs, and provide novel insights into the immune-modulatory role of testosterone in sex differential IFN-I-mediated immune responses.

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Project description:Plasmacytoid dendritic cells (pDCs) are a rare type of dendritic cells that exist antiviral functions in response to toll-like receptors (TLRs). We here report TLR4 activated pDCs similar to TLR7/8 stimulation. Despite the high resemblance, we found the unique genes that were activated by TLR4 activation.

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Gene expression changes in neonatal and adult plasmacytoid dendritic cells (pDC) upon TLR7/8 stimulation

Project description:We want to define the differences in gene expression changes between neonatal and adult plasmacytoid dendritic cells upon stimulation with TLR7/8. These differences may point to specific signaling pathways which, in turn, may account for the known differential immune response of babies to vaccination or infection when compared to adults.

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Plasmacytoid dendritic cell heterogeneity is defined by CXCL10 expression following TLR7 stimulation

Project description:Plasmacytoid dendritic cells (pDCs) play a critical role in bridging the innate and adaptive immune systems. pDCs are specialized type I interferon (IFN) producers, which has implicated them as initiators of autoimmune pathogenesis. However, little is known about the down-stream effectors of type I IFN signaling that amplify autoimmune responses. Here we have used a chemokine reporter mouse to determine the CXCR3 ligand responses in DCs subsets. Following TLR7 stimulation conventional type 1 and type 2 DCs (cDC1 and cDC2 respectively) uniformly upregulate CXCL10. By contrast, the proportion of chemokine positive pDCs was significantly less, and stable CXCL10+ and CXCL10 - populations could be distinguished. CXCL9 expression was induced in all cDC1s, in half of the cDC2 but not by pDCs. In all DC subsets, type I IFNs were the main inducer of CXCR3 chemokines, as IFNAR receptor blocking or deficiency completely abrogated reporter expression. Chemoki ne producing potential was not concordant with the previously identified markers of pDC heterogeneity. Finally, we show that CXCL10+ and CXCL10 - populations are transcriptionally distinct, expressing unique transcriptional regulators, IFN signaling molecules, chemokines, cytokines and cell surface markers. This work highlights CXCL10 as a downstream effector of type I IFN signaling and suggests a division of labor in pDCs subtypes that likely impacts their function as effectors of viral responses and as drivers of inflammation.

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Plasmacytoid dendritic cell heterogeneity is defined by CXCL10 expression following TLR7 stimulation

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Reduction of TLR7/8-Induced IFN-I Responses by Plasmacytoid Dendritic Cells in a Longitudinal Cohort of Trans Men

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TLR7 sensing of SARS-CoV-2 and IFN-I response by plasmacytoid dendritic cells leads to the hyperactivation of macrophages.

Project description:TLR7 sensing of SARS-CoV-2 and IFN-I response by plasmacytoid dendritic cells leads to the hyperactivation of macrophages.