RNA-seq of human type 2 innate lymphoid cells (ILC2) stimulated with PGD2 or PGD2 metabolites (Δ12PGJ2, Δ12PGD2, 15-deoxyΔ12,14PGD2, 9α,11β-PGF2) with or without the selective DP2 antagonist fevipiprant
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina NovaSeq 6000
ORGANISM(S): Homo sapiens
SUBMITTER: Christina Gress
PROVIDER: E-MTAB-13623 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Segmental instillation of lipopolysaccharide (LPS) by bronchoscopy can be used as a model to safely induce transient airway inflammation in the human lung. The LPS challenge model enables investigation of cellular mechanisms involved in pulmonary inflammatory processes as well as pharmacodynamic analysis of investigational drugs for the treatment of respiratory diseases. Aim of this work was to describe the transcriptomic profile of the human segmental LPS challenge model with contextualization to major respiratory diseases. Pre-challenge bronchoalveolar lavage fluid (BAL) and biopsies were sampled from twenty-eight smoking, healthy subjects, followed by segmental LPS challenge and saline control challenge. Twenty-four hours post instillation, BAL and biopsies were collected from the challenged lung segments. Total RNA of cells from BAL and biopsy samples were sequenced for subsequent data analysis. Differential gene expression analysis resulted in 6316 upregulated differentially expressed genes (DEGs) and 241 downregulated DEG in BAL, but only one downregulated DEG in biopsy samples after LPS challenge compared to saline challenge. Upregulated DEG in BAL were related to molecular functions such as “Inflammatory response” or “antimicrobial humoral immune response mediated by antimicrobial peptide”, enriched biological processes such as “chemokine receptor activity”, and upregulated pro-inflammatory pathways such as “Wnt signaling pathway”, “Ras signaling pathway” or “JAK-STAT signaling pathway”. Furthermore, the segmental LPS challenge model resembled aspects of the five most prevalent respiratory diseases chronic obstructive pulmonary disease (COPD), asthma, pneumonia, tuberculosis and lung cancer and featured similarities with acute exacerbations in COPD (AECOPD) and community-acquired pneumonia (CAP). Overall, our study provides extensive information about the transcriptomic profile from BAL cells and mucosal biopsies following LPS challenge in healthy smokers. It expands the knowledge about the LPS challenge model providing potential overlap with respiratory diseases in general and infection-triggered respiratory insults such as AECOPD in particular.
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Project description:T cells undergo autoimmunization following spinal cord injury (SCI) and play both protective and destructive roles during the recovery process. T-cell deficient athymic nude (AN) rats recover better than immunocompetent Sprague-Dawley (SD) rats following spinal cord transection. In the present study, we evaluated locomotor recovery in SD and AN rats following moderate spinal cord contusion. To explain variable locomotor outcome, we assessed whole-genome expression using RNA sequencing, in the acute (1 week post-injury) and chronic (8 weeks post-injury) phases of recovery. AN rats demonstrated greater locomotor function than SD rats only at 1 week post-injury, coinciding with peak T cell infiltration in immunocompetent rats. Genetic markers for T cells and helper T cells were acutely enriched in SD rats, while AN rats expressed genes for Th2 cells, cytotoxic T cells, NK cells, mast cells, IL-1a, and IL-6 at higher levels. Acute enrichment of cell death-related genes suggested that SD rats undergo secondary tissue damage from T cells. Additionally, SD rats exhibited increased acute expression of voltage-gated potassium (Kv) channel-related genes. However, AN rats demonstrated greater chronic expression of cell death-associated genes and less expression of axon-related genes. We put forth a model in which T cells facilitate early tissue damage, demyelination, and Kv channel dysregulation in SD rats following contusion SCI. However, compensatory features of the immune response in AN rats cause delayed tissue death and limit long-term recovery. T cell inhibition combined with other neuroprotective treatment may thus be a promising therapeutic avenue. 2x2 model with 4 groups and 12 total samples. 2 rat strains (athymic nude [AN] and Sprague-Dawley [SD]) and 2 time points (1 week post-injury [acute] and 8 weeks post-injury [chronic]). 3 samples per group, for a total of 12 samples. No technical replicates were performed. Acute SD group = rats 618, 619, and 620. Chronic SD group = rats 605, 606, and 608. Acute AN group = rats 714, 715, and 717. Chronic AN group = rats 707, 712, and 713.
2015-10-26 | E-GEOD-62760 | biostudies-arrayexpress
Project description:Systems responses of mature leaves from 4 reference cultivars of a larger collection of European potato cultivars (Solanum tuberosum L.) are investigated by metabolome profiling and RNA-Sequencing. The chosen reference cultivars, Milva, Alegria, Desiree, and Saturna, vary in ascending order in regard to drought tolerance. Systems analyses are based on 3 independent field trials and 3 paralleled greenhouse trials. Robust responses across all cultivars and conditions to natural seasonal drought stress comprise proline, raffinose, galactinol, arabitol, arabinonic acid, chlorogenic acid, and 102 transcripts which consist to a high proportion of heat shock proteins and genes with signaling or regulatory functions, such as a homolog of abscisic acid receptor PYL4. Constitutive differences of the tolerant cultivars, Desiree and Saturna, compared to the sensitive cultivars include arbutin (hydroquinone-beta-D-glucopyranoside), octopamine (p-hydroxyphenylethanolamine), ribitol and 248 differential transcripts. Many of these transcripts are disease related, receptor kinases, or regulatory genes, for example a homolog of the Arabidopsis FOUR LIPS MYB-regulator of stomatal cell proliferation. Functional enrichment analyses imply that heat stress is a major acclimation component of potato leaves to agronomical relevant drought stress. Enhanced leaf heat stress is a result of drought caused by loss of transpiration cooling. This effect and CO2-limitation are the main dilemmas of drought- or ABA-induced stomatal closure. Constitutive differences between tolerant and sensitive cultivars indicate partially synergistic interactions of drought and biotic stress responses. We suggest that drought tolerance of the potato reference cultivars may be caused by general resistance mechanisms which are part of previously selected pathogen tolerance. Transcriptome profiling by RNA-sequencing of 48 leaf samples from 4 potato cultivars grown under control or drought stress conditions in 6 independent experiments
2016-07-06 | E-GEOD-77826 | biostudies-arrayexpress
Project description:This experiment sought to determine whether estrogen could directly activate changes in gene transcription in lung and uterine ILC2s, whether such changes differed between lung and uterine ILC2s, and compared baseline gene expression between ILC2s from those organs. ILC2s, defined as lineage (CD3e, CD14, CD16/32 and B220) negative, CD25 positive and CD44 high lymphocytes, were sorted by flow cytometry from 8-12 week old BALB/c mice and cultured overnight in RPMI 1640 with 10% charcoal/dextran treated calf serum in the absence or presence of 100 ng/ml estrogen. RNA was extracted from the cells after culture.
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2012-03-26 | E-GEOD-36169 | biostudies-arrayexpress
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2017-07-03 | E-MTAB-3908 | biostudies-arrayexpress
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2013-10-20 | E-GEOD-45621 | biostudies-arrayexpress