Similar Datasets
Project description:We found that cardiac fibroblasts produce and secrete exosomes. miRNA profiling and TaqMan qRT-PCR experiments identified miR-21 expression to be higher in cardiac fibroblasts compared to those of miR-21*, whereas in exosomes miR-21* expression was higher compared to miR-21. The purpose of the study was to validate these findings by miRNA sequencing in cardiac fibroblasts and fibroblasts-derived exosomes.
2015-12-19 | GSE76175 | GEO
Project description:Interleukin-21 (IL-21) has broad actions on T- and B-cells, but its actions in innate immunity are poorly understood. Here we show that IL-21 induced apoptosis of conventional dendritic cells (cDCs) via STAT3 and Bim, and this was inhibited by granulocyte-macrophage colony-stimulating factor (GM-CSF). ChIP-Seq analysis revealed genome-wide binding competition between GM-CSF-induced STAT5 and IL-21-induced STAT3. Expression of IL-21 in vivo decreased cDC numbers, and this was prevented by GM-CSF. Moreover, repetitive α-galactosylceramide injection of mice induced IL-21 but decreased GM-CSF production by natural killer T (NKT) cells, correlating with decreased cDC numbers. Furthermore, adoptive-transfer of wild-type CD4+ T cells caused more severe colitis with increased DCs and interferon (IFN)-γ-producing CD4+ T cells in Il21r-/-Rag2-/- mice (which lack T cells and have IL-21-unresponsive DCs) than in Rag2-/- mice. Thus, IL-21 and GM-CSF exhibit cross-regulatory actions on gene regulation and apoptosis, regulating cDC numbers and thereby the magnitude of the immune response.
2013-02-14 | GSE27161 | GEO
Project description:In grasses, 21- and 24-nt phasiRNAs are abundantly expressed in anthers and play crucial roles in anther development and male reproduction. 21-nt phasiRNAs can act in cis to direct the cleavage of their own precursor transcripts and is thought to lack trans cleavage targets in maize. Here we show that 21-nt phasiRNAs direct the cleavage of hundreds of target mRNAs in maize, with the cleavage activity being enriched in male germ cells. Interestingly, whereas 21-nt phasiRNAs in anthers (somatic anther wall cells) do not have obvious preference for a particular nucleotide at the 5’ end and target genes implicated in stress response and cellular homeostasis, 21-nt phasiRNAs in male germ cells preferentially initiate with 5’ C and associate with ZmAGO5c/MAGO2/MS28 to target genes related to meiotic processes. Our results indicate that mRNA cleavage is a conserved mechanism used by 21-nt phasiRNAs for gene regulation. However, the sequences of 21-nt phasiRNAs and their targets show low conservation in maize and rice, suggesting that 21PHAS loci and 21-nt phasiRNA targets have undergone fast divergence in monocots.
2025-05-26 | GSE279862 | GEO
Project description:Interleukin-21 (IL-21) is a pleiotropic cytokine that induces expression of transcription factor BLIMP1 (encoded by Prdm1), which regulates plasma cell differentiation and T cell homeostasis. We identified an IL-21 response element downstream of Prdm1 that binds the transcription factors STAT3 and IRF4, which are required for optimal Prdm1 expression. Genome-wide ChIP-Seq mapping of STAT3- and IRF4-binding sites showed that most regions with IL-21-induced STAT3 binding also bound IRF4 in vivo, and furthermore, revealed that the noncanonical TTCnnnTAA GAS motif critical in Prdm1 was broadly used for STAT3 binding. Comparing genome-wide expression array data to binding sites revealed that most IL-21-regulated genes were associated with combined STAT3-IRF4 sites rather than pure STAT3 sites. Correspondingly, ChIP-Seq analysis of Irf4_/_ T cells showed greatly diminished STAT3 binding after IL-21 treatment, and Irf4_/_ mice showed impaired IL- 21-induced Tfh cell differentiation in vivo. These results reveal broad cooperative gene regulation by STAT3 and IRF4. Affymetrix expression data: Prepare CD4+ T cells from spleen. CD4+ T cells were preactivated, rested, and treated with IL-21 for 1, 6, and 24 hours. ChIP-seq data: Profiling of IRF4 and Stat3 binding with and without IL-21 stimulation in wild type and IRF4 KO mice.
2010-01-08 | E-GEOD-19198 | biostudies-arrayexpress
Project description:Interleukin-21 (IL-21) has broad actions on T- and B-cells, but its actions in innate immunity are poorly understood. Here we show that IL-21 induced apoptosis of conventional dendritic cells (cDCs) via STAT3 and Bim, and this was inhibited by granulocyte-macrophage colony-stimulating factor (GM-CSF). ChIP-Seq analysis revealed genome-wide binding competition between GM-CSF-induced STAT5 and IL-21-induced STAT3. Expression of IL-21 in vivo decreased cDC numbers, and this was prevented by GM-CSF. Moreover, repetitive M-NM-1-galactosylceramide injection of mice induced IL-21 but decreased GM-CSF production by natural killer T (NKT) cells, correlating with decreased cDC numbers. Furthermore, adoptive-transfer of wild-type CD4+ T cells caused more severe colitis with increased DCs and interferon (IFN)-M-NM-3-producing CD4+ T cells in Il21r-/-Rag2-/- mice (which lack T cells and have IL-21-unresponsive DCs) than in Rag2-/- mice. Thus, IL-21 and GM-CSF exhibit cross-regulatory actions on gene regulation and apoptosis, regulating cDC numbers and thereby the magnitude of the immune response. Total 6 samples were examined. Splenic dendritic cells were treated with IL-21 and/or GM-CSF studying STAT3 and STAT5B binding in the genome
2013-02-14 | E-GEOD-27161 | biostudies-arrayexpress
Project description:The cytokine interleukin-21 (IL-21) is a pivotal T cell-derived signal crucial for germinal center (GC) responses, but the precise mechanisms by which IL-21 influences B cell function remain elusive. Here, we investigated the B cell-intrinsic role of IL-21 signaling by employing a novel IL-21 receptor (Il21r) conditional knock-out mouse model and ex vivo culture systems and uncovered a surprising duality of IL-21 signaling in B cells. While IL-21 stimulation of naïve B cells led to Bim-dependent apoptosis, it promoted robust proliferation of pre-activated B cells, particularly class-switched IgG1+ B cells ex vivo. Consistent with this, B cell-specific deletion of Il21r led to a severe defect in IgG1 responses in vivo following immunization. Intriguingly, Il21r-deleted B cells are significantly impaired in their ability to transition from a pre-GC to a GC state following immunization. Although Il21r-deficiency did not affect the proportion of IgG1+ B cells among GC B cells, it greatly diminished the proportion of IgG1+ B cells among the plasmablast/plasma cell population. Collectively, our data suggest that IL-21 serves as a critical regulator of B cell fates, influencing B cell apoptosis and proliferation in a context-dependent manner.
2025-01-01 | GSE280837 | GEO
Project description:Exosomes from the brains of rhesus macaques were isolated and characterized, both with and without simian immunodeficiency virus (SIV) induced central nervous system (CNS) disease. Small RNA sequencing revealed that exosomes from the brains of animals with CNS disease contained significantly increased miR-21, a microRNA we have previously shown to be significantly increased in both SIV and HIV induced CNS disease. In addition to neurons in the brain, macrophage/microglial cells/nodules also express miR-21 during SIV induced CNS disease. In vitro culture of macrophages revealed that miR-21 is released into exosomes, and exosomes from macrophage cultures produced from WT, but not miR-21-/- KO, animals are neurotoxic. We find this neurotoxicity is dependent upon exosome carriage of miR-21, and mutation of the sequence within miR-21 predicted to bind TLR7 eliminates this neurotoxicity. Indeed exosomal miR-21 activates TLR7 in a reporter cell line, and the neurotoxicity of exosomal miR-21 is dependent upon TLR7, as neurons isolated from TLR7-/- KO mice are protected from neurotoxicity. Finally, we show that exosomes isolated from the brains of monkeys with SIV induced CNS disease both activate TLR7 and are neurotoxic when compared to exosomes from control animals.
2018-01-29 | GSE109414 | GEO
Project description:The canonical pathway for IL-1β production requires TLR-mediated NF-κB-dependent Il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-IL-1β. Here we show that IL-21 unexpectedly induces IL-1β production in conventional dendritic cells (cDCs) via a STAT3-dependent but NF-κB-independent pathway. IL-21 does not induce Il1b expression in CD4+ T cells, with differential histone marks present in these cells versus cDCs. IL-21-induced IL-1β processing in cDCs does not require caspase-1 or caspase-8 but depends on IL-21-mediated death and activation of serine protease(s). Moreover, STAT3-dependent IL-1β expression in cDCs at least partially explains the IL-21-mediated pathologic response occurring during infection with Pneumonia Virus of Mice. These results demonstrate lineage-restricted IL-21-induced IL-1β via a non-canonical pathway and provide evidence for its importance in vivo.
2015-07-07 | GSE61677 | GEO
Project description:Approximately 15% of lung cancer cases are not associated with smoking and show molecular and clinical characteristics distinct from those in smokers. Epidermal growth factor receptor (EGFR) gene mutations, which are correlated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), are more frequent in never-smoker lung cancers. In this study, microRNA (miRNA) expression profiling of 28 never-smoker lung cancer cases identified aberrantly expressed miRNAs, which were much fewer than in lung cancers of smokers and included miRNAs previously identified (e.g., upregulated miR-21) and unidentified (e.g., downregulated miR-138) in those smoker cases. The changes in expression of some of these miRNAs were more remarkable in cases with EGFR mutations than in those without: the most upregulated miRNA, miR-21, was more abundant in cancers with EGFR mutation. A significant correlation between phosphorylated-EGFR (p-EGFR) and miR-21 levels in lung carcinoma cell lines and the suppression of miR-21 by an EGFR-TKI, AG1478, suggested that the EGFR signaling pathway positively regulated miR-21 expression. In a never-smoker-derived lung adenocarcinoma cell line H3255 with mutant EGFR and high levels of p-EGFR and miR-21, antisense inhibition of miR-21 enhanced AG1478-induced apoptosis. In a never-smoker-derived adenocarcinoma cell line H441 with wild-type EGFR, the antisense miR-21 not only showed the additive effect with AG1478 but also induced apoptosis by itself. These results suggest that aberrantly increased expression of miR-21, which is further enhanced by the activated EGFR signaling pathway, plays a critical role in lung carcinogenesis in never-smokers and is a potential therapeutic target in both EGFR mutant and wild-type cases.
2009-07-29 | GSE14936 | GEO
Project description:The osdcl4-1 mutant exhibits much severer developmental defects than dcl4 in Arabidopsis, suggesting that Os DCL4 may process broader substrates in rice. By deep sequencing of small RNAs from different tissues of wild types and osdcl4-1, we revealed that 21-nucleotide siRNAs were largely dependent on Os DCL4. Besides several tasiRNA loci reported in Arabidopsis and rice, over one thousand 21-nucleotide and several dozen 24-nucleotide phased siRNA (phasiRNA) clusters were identified in panicles but not in seedlings and grains. Further analyses identified two conserved 22-nucleotide motifs among the cleavage sites of the 21- and 24- phasiRNA loci, and the cleavage sites of over 90% of 21- and 24-nucleotide phasing clusters were confirmed by PARE/degradome analysis from 93-11 panicles. MiR2118 and miR2275, expressed specifically in panicles, were predicted to trigger cleavages at 21- and 24-nucleotide phasiRNA clusters, respectively. The triggers of phasiRNAs are more dependent on Os DCL4 than Os DCL1. Furthermore, the processing of 21-nucleotide phasiRNAs was largely Os DCL4-dependent, whereas the processing of 24-nucleotide phasiRNAs was slightly affected by Os DCL4, but not by Os DCL3a and Os DCL1. Our results revealed distinct roles of Os DCL4 in a novel 21- and 24-nucleotide phasiRNA biogenesis pathway in rice.
2012-03-30 | GSE22763 | GEO