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Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare distinct immunostimulatory activities of three classes of CpG ODNs in pDCs using RNA-seq. mRNA profiles of murine pDCs induced by three classes of CpG ODNs were generated by RNA-Seq studies. Methods: mRNA profiles of murine pDCs induced by three classes of CpG ODNs were generated by deep sequencing, in triplicate, using Illumina Hiseq Xten. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: HISAT based on Burrows-Wheeler transform and Ferragina-Manzini and Bowtie2 followed by RSEM. Results: Using an optimized data analysis workflow, we mapped > 60 million total clean reads per sample to the mouse genome (build mm10), with a clean reads Q20 score > 98.58% and a mapping rate to the reference genome of each sample varying from 92.3% to 96.56%. The Pearson correlation coefficient between each sample revealed that CpG-A and CpG-C have the highest correlation. A total of 21,573 genes were detected as being expressed. More than 5,000 genes were downregulated and 2,000 genes were upregulated in CpG ODNs stimulated groups relative to control group, with a fold change ≥ 2 and Q value <0.001. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed genes uncovered several genes that may contribute to characterize the features of three classes of CpG ODNs in pDCs. Conclusions: Our study represents the first detailed analysis of pDC transcriptomes stimulated with three classes of CpG ODNs, with biological replicates, generated by RNA-seq technology.
2022-12-24 | GSE142688 | GEO
Project description:Characterization of three CpG ODN classes in plasmacytoid dendritic cells (pDCs)
| PRJNA597989 | ENA
Project description:Characterization of three CpG ODN classes in plasmacytoid dendritic cells and B cells
| PRJNA597991 | ENA
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare distinct immunostimulatory activities of three classes of CpG ODNs in B cells using RNA-seq. mRNA profiles of murine B cells induced by three classes of CpG ODNs were generated by RNA-Seq studies. Methods: mRNA profiles of murine B cells induced by three classes of CpG ODNs were generated by deep sequencing, in triplicate, using BGISEQ. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: HISAT based on Burrows-Wheeler transform and Ferragina-Manzini and Bowtie2 followed by RSEM. Results: Using an optimized data analysis workflow, we mapped > 60 million total clean reads per sample to the mouse genome (build mm10), with a clean reads Q20 score >97% and a mapping rate to the reference genome of each sample varying from 89.33% to 93.29%. The Pearson correlation coefficient between each sample revealed that the all samples had a high correlation. In particular, CpG-B and CpG-C have the highest correlation. A total of 28,020 genes were detected as being expressed. More than 10,000 genes were downregulated and 1,000 genes were upregulated in CpG ODNs stimulated groups relative to control group, with a fold change ≥ 2 and Q value <0.001. In addition, only 91 genes were upregulated and 99 genes were downregulated in CpG-C group relative to CpG-B group. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed genes uncovered several genes that may contribute to characterize the features of three classes of CpG ODNs in B cells. Conclusions: Our study represents the first detailed analysis of B-cell transcriptomes stimulated with three classes of CpG ODNs, with biological replicates, generated by RNA-seq technology.
2022-12-24 | GSE142689 | GEO
Project description:Characterization of three CpG ODN classes in B cells
| PRJNA597990 | ENA
Project description:Topical microbicides represent a promising new approach to preventing HIV and other sexually transmitted infections. TLR agonists are ideal candidates for microbicides, as they trigger a multitude of antiviral genes effective against a broad range of viruses. Although vaginal application of CpG oligodeoxynucleotides (ODNs) and poly I:C has been shown to protect mice from genital herpes infection, the mechanism by which these agents provide protection remains unclear. Here, we show that plasmacytoid DCs (pDCs) are required for CpG ODN-mediated protection against lethal vaginal challenge with herpes simplex virus type 2 (HSV-2). Moreover, we demonstrate that cells of both the hematopoietic and stromal compartments must respond to CpG ODN via TLR9 and to type I IFNs through IFN-alphabeta receptor (IFN-alphabetaR) for protection. Thus, crosstalk between pDCs and vaginal stromal cells provides for optimal microbicide efficacy. Our results imply that temporally and spatially controlled targeting of CpG ODN to pDCs and epithelial cells can potentially maximize their effectiveness as microbicides while minimizing the associated inflammatory responses.
| S-EPMC1518794 | biostudies-literature
Project description:Plasmacytoid dendritic cells (pDC) compose 0.2-0.5% of circulating leukocytes but play a significant role in mounting host immune responses. Elevated and chronic activation of pDC are implicated in autoimmune disease like systemic lupus erythematosus and rheumatoid arthritis. ?9-tetrahydrocannabinol (THC) is a well characterized cannabinoid with potent anti-inflammatory activity, but acceptance of THC as a treatment for autoimmune disorders has been hindered due to psychotropic activity. The psychotropic effects of THC are mediated through cannabinoid receptor 1 (CB1) expressed in the central nervous system while the immunomodulatory effects of THC result from THC binding to CB1 and CB2 on immune cells. Synthetic CB2-selective agonists have been developed to explore immune modulation by cannabinoids in the absence of psychotropic effects. The goal of these studies was to determine if the CB2-selective agonists, JWH-015 and JWH-133, have comparable efficacy to THC in modulating IFN? and TNF? responses by primary human pDC. Treatment with JWH-133 and JWH-015 inhibited CpG-induced IFN? and TNF? responses by pDC. Further, the phosphorylation of IRF7, TBK1, NF?B, and IKK?, key events in pDC activation, were suppressed by THC, JWH-133, and JWH-015. Likewise, the phosphorylation of AKT at the S473 and T308 residues were differentially modulated by treatment with THC and both JWH compounds. Collectively, these results demonstrate the potential for CB2 targeted therapeutics for treatment of inflammatory conditions involving aberrant pDC activity.
| S-EPMC7243911 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2011-04-01 | GSE23491 | GEO
Project description:Gender differences in immune capabilities suggest that sex hormones such as estrogens were involved in the regulation of the immunocompetence. Numerous studies also suggest that plasmacytoid dendritic cells (PDCs) play a pathogenic role in SLE. However, it is unclear whether estrogen can modulate the function of PDCs to influence the development of SLE. In the present study, PDCs from murine spleens were treated with 17beta-estradiol (E2) and CpG respectively or both in vitro, then cell viability, costimulatory molecule expression, cytokine secretion of PDCs, as well as stimulatory capacity of PDCs to B cells were analyzed. Results showed that E2 and CpG increased the cell viability and costimulatory molecule expression on PDCs synergistically. Moreover, the intracellular and extracellular secretion of IFN-alpha was increased by E2 or E2 plus CpG. In addition, E2 and CpG also increased the stimulatory capacity of PDCs to B cells, and the viability of B cells was decreased after neutralizing IFN-alpha significantly. In the experiments in vivo, mice received daily s.c. injections of E2 and CpG respectively or both, then we found that the plasma concentration of IgM were elevated by E2 and CpG synergistically and the expression of IFN-alpha/beta in spleens were noticeably increased by CpG plus E2 compared with the treatment of E2 or CpG only. This study indicates that E2 could exacerbate PDCs' activation with CpG, which further activates B cells to upregulate susceptibility to autoantigens. IFN-alpha plays an important role in the stimulatory effect of PDCs on B cells. E2 stimulation of IFN-alpha production may result in female prevalence in autoimmune diseases such as SLE through activation of PDCs. This study provides novel evidence of relationship between estrogen and SLE and also sheds light on gender biases among SLE patients.
| S-EPMC2793013 | biostudies-other
Project description:BackgroundHuman plasmacytoid dendritic cells (pDC) have a dual role as interferon-producing and antigen-presenting cells. Their relevance for allergic diseases is controversial. and the impact of pDC on allergic immune responses is poorly understood.MethodsThis in vitro study on human pDC isolated from peripheral blood was designed to compare side by side the uptake of three clinically relevant representative allergens: fluorochrome-labeled house dust mite Der p 1, Bee venom extract from Apis mellifera (Api) and the food allergen OVA analyzed flow cytometry and confocal microscopy.ResultsWe found that the internalization and its regulation by TLR9 ligation was significantly different between allergens in terms of time course and strength of uptake. Api and OVA uptake in pDC of healthy subjects was faster and reached higher levels than Der p 1 uptake. CpG ODN 2006 suppressed OVA uptake and to a lesser extent Der p 1, while Api internalization was not affected. All allergens colocalized with LAMP1 and EEA1, with Api being internalized particularly fast and reaching highest intracellular levels in pDC. Of note, we could not determine any specific differences in antigen uptake in allergic compared with healthy subjects.ConclusionsTo our knowledge this is the first study that directly compares uptake regulation of clinically relevant inhalative, injective and food allergens in pDC. Our findings may help to explain differences in the onset and severity of allergic reactions as well as in the efficiency of AIT.
| S-EPMC8597288 | biostudies-literature