Pattern recognition receptors (PRR) detect microbial products and induce cytokines which shape the immunological response. Interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-) and IL-1 are proinflammatory cytokines which can be essential for resistance against infection, but if produced at high levels, may contribute to immunopathology. In contrast, IL-10 is an immunosuppressive cytokine which dampens proinflammatory responses, but can also lead to defective pathogen clearance. The regulation of these cytokines is therefore central to the generation of an effective but balanced immune response. Here, we show that macrophages derived from C57BL/6 mice produce low levels of IL-12, TNF- and IL-1, but high levels of IL-10 in response to TLR4 and TLR2 ligands LPS and PamCSK4, and Burkholderia pseudomallei a Gram-negative bacterium which activates TLR 2/4. In contrast, macrophages derived from BALB/c mice show a reciprocal pattern of cytokine production. Differential production of IL-10 in B. pseudomallei and LPS stimulated C57BL/6 and BALB/c macrophages was due to a type I IFN dependent, but IL-27 independent mechanism. Further, type I IFN contributed to differential IL-1 and IL-12 production in B. pseudomallei and LPS stimulated C57BL/6 and BALB/c macrophages, via both IL-10-dependent and independent mechanisms. These findings highlight key pathways responsible for the regulation of pro- and anti-inflammatory cytokines in macrophages and reveal how they may differ according to the genetic background of the host.
Differential Production of Type I IFN Determines the Reciprocal Levels of IL-10 and Proinflammatory Cytokines Produced by C57BL/6 and BALB/c Macrophages.
Sex, Specimen part, Treatment, Time
View SamplesAsthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues including epithelial and T cells.
Multitissue Transcriptomics Delineates the Diversity of Airway T Cell Functions in Asthma.
Sex, Subject
View SamplesManagement of severe asthma remains a challenge despite treatment with glucocorticosteroid therapy. The majority of studies investigating disease mechanisms in treatment-resistant severe asthma have previously focused on the large central airways, with very few utilizing transcriptomic approaches. The small peripheral airways, which comprise the majority of the airway surface area, remain an unexplored area in severe asthma and were targeted for global epithelial gene expression profiling in this study.
Altered Epithelial Gene Expression in Peripheral Airways of Severe Asthma.
Sex, Age, Specimen part, Disease, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene.
Cell line, Treatment, Time
View SamplesTotal RNA was isolated from liver samples of C57/BL6 mice over a circadian time course, 3 biological replicate samples per time point were collected and processed individually. RNA from each individual biological replicate sample was extracted using RNeasy mini kit (Qiagen Cat# 74106) and hybridized on an Affymetrix mouse Gene ST1.0 microarray.
Histone methyltransferase MLL3 contributes to genome-scale circadian transcription.
Specimen part, Time
View SamplesIntegration of multi-omics data remains a key challenge in fulfilling the potential of comprehensive systems biology.
OnPLS-Based Multi-Block Data Integration: A Multivariate Approach to Interrogating Biological Interactions in Asthma.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesPlasmodium berghei ANKA infection in mice is used as a model for human cerebral malaria, the most severe complication of Plasmodium falciparum infection. The response of brain cells such as microglia has been little investigated, and may play a role in the pathogenesis or regulation of cerebral malaria. We showed previously that microglia are activated in P. berghei infections, and that Type 1 Interferon signaling is important for activation. This dataset contains the transcriptome of brain microglia of infected mice in the presence and absence of Type I interferon signaling, with the aim of identifying the genes involved in this pathway in microglia during experimental cerebral malaria. Refererence: Capuccini et al 2016, Scientific Reports, 6:39258
Transcriptomic profiling of microglia reveals signatures of cell activation and immune response, during experimental cerebral malaria.
Sex, Specimen part, Treatment
View SamplesGene expression in larval, early third instar eye-antenna discs was assessed to reveal an ATF4 contribution to target gene induction following COX7a knockdown. As hypothesised, these COX7a-RNAi induced target genes require the transcription factor ATF4 for induction, irrespective of concomitant Notch pathway activation through Delta over-expression.
ATF4-Induced Warburg Metabolism Drives Over-Proliferation in Drosophila.
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View SamplesThe transcription-related DNA damage response was analyzed on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a slowdown of transcript elongation and restriction of gene activity to the promoter-proximal ~25 kilobases is observed. This is associated with a shift from expression of long mRNAs to shorter isoforms, incorporating alternative last exons (ALEs) that are more proximal to the transcription start site. Notably, this includes a shift from a protein-coding ASCC3 mRNA to a shorter transcript isoform of which the RNA, rather than an encoded protein, is critical for the eventual recovery of transcription. The protein-coding ASCC3 isoform counteracts the function of the non-coding isoform, indicating crosstalk between them. Thus, the ASCC3 gene expresses both coding and noncoding transcript isoforms with opposite effects on transcription recovery after UV-induced DNA damage
UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene.
Cell line, Treatment, Time
View SamplesThe transcription-related DNA damage response was analyzed on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a slowdown of transcript elongation and restriction of gene activity to the promoter-proximal ~25 kilobases is observed. This is associated with a shift from expression of long mRNAs to shorter isoforms, incorporating alternative last exons (ALEs) that are more proximal to the transcription start site. Notably, this includes a shift from a protein-coding ASCC3 mRNA to a shorter transcript isoform of which the RNA, rather than an encoded protein, is critical for the eventual recovery of transcription. The protein-coding ASCC3 isoform counteracts the function of the non-coding isoform, indicating crosstalk between them. Thus, the ASCC3 gene expresses both coding and noncoding transcript isoforms with opposite effects on transcription recovery after UV-induced DNA damage
UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene.
Cell line, Treatment, Time
View Samples