The encapsulated yeast Cryptococcus neoformans can cause a fatal meningoencephalitis in immunocompromised patients. C. neoformans infection is acquired through the respiratory tract, but the cellular and molecular mechanisms of the pulmonary innate immune response are still not well defined. To investigate the response of CCR2+ inflammatory monocytes to C. neoformans, we compared the transcriptomes of CCR2+ inflammatory monocytes from the lungs of naïve versus infected mice. Overall design: Sorted pulmonary CCR2+ inflammatory monocytes were pooled from 6-7 CCR2-GFP reporter mice per group, including naïve mice and mice challenged with intratracheal Cryptococcus neoformans on days 5 and 10 post-infection.
Inflammatory monocytes are detrimental to the host immune response during acute infection with Cryptococcus neoformans.
Specimen part, Cell line, Subject
View SamplesThe Nrf2 transcription factor is a key player in the cellular stress response, which regulates the expression of important antioxidant enzymes and other cytoprotective proteins. We recently generated a novel transgenic mouse model to determine the function of Nrf2 in the skin. These mice revealed interesting phenotypic abnormalities, including hyperkeratosis and acanthosis. To gain insight into the underlying molecular mechanisms, we wanted to identify genes, which are differentially expressed in the skin of wild-type and mutant mice before the onset of phenotypic abnormalities.
Nrf2 links epidermal barrier function with antioxidant defense.
Sex, Treatment
View SamplesWe have shown that activin promoted skin tumorigenesis in mice induced by the human papilloma virus 8 oncogenes. Activin attracted blood monocytes to the skin as revealed by depletion of CCR2-positive monocytes. To determine if activin also altered the gene expression profile of these cells, we performed RNA-Sequencing of macrophages FACS-sorted from the pre-cancerous ear skin. We have found that activin induces a pro-migratiory, pro-angiogenic and pro-tumorigenic genes in skin macrophages in vivo. This largely contributes to the pro-tumorigenic function of activin, since macrophage depletion delayed spontaneous tumorigenesis in HPV8-transgenic mice by reducing keratinocyte proliferation and angiogenesis. Overall design: F4/80+CD11b+CD45+ cells were FACS-sorted from the pre-cancerous ear skin of wt/wt, HPV8/wt, wt/Act and HPV8/Act mice and their expression profile was analysed by RNA-Sequencing. Experiment was performed in triplicates, for each replicate ear skin of 3-6 mice of corresponding genotype was pooled.
Activin promotes skin carcinogenesis by attraction and reprogramming of macrophages.
Specimen part, Cell line, Subject
View SamplesC5aR1, a receptor for the complement activation proinflammatory fragment, C5a, is primarily expressed on cells of the myeloid lineage, and to a lesser extent on endothelial cells and neurons in brain. Previous work demonstrated C5aR1 antagonist, PMX205, decreased amyloid pathology and suppressed cognitive deficits in Alzheimer Disease (AD) mouse models. In the Arctic AD mouse model, genetic deletion of C5aR1 prevented behavior deficits at 10 months. However, the molecular mechanisms of this protection has not been definitively demonstrated. To understand the role of microglial C5aR1 in the Arctic AD mouse model, we have taken advantage of the CX3CR1GFP and CCR2RFP reporter mice to distinguish microglia as GFP-positive and infiltrating monocytes as GFP and RFP positive, for subsequent transcriptome analysis on specifically sorted myeloid populations from wild type and AD mouse models. Immunohistochemical analysis of mice aged to 2, 5, 7 and 10 months showed no change in amyloid beta (Ab) deposition in the Arctic C5aR1 knockout (KO) mice relative to that seen in the Arctic mice. Of importance, no CCR2+ monocytes/macrophages were found near the plaques in the Arctic brain with or without C5aR1. RNA-seq analysis on microglia from these mice identified inflammation related genes as differentially expressed, with increased expression in the Arctic mice relative to wildtype and decreased expression in the Arctic/C5aR1KO relative to Arctic. In addition, phagosomal-lysosomal proteins and protein degradation pathways that were increased in the Arctic mice were further increased in the Arctic/C5aR1KO mice. These data are consistent with a microglial polarization state with restricted induction of inflammatory genes and enhancement of clearance pathways. Overall design: Microglia mRNA profiles of wildtype (WT), C5aR1 knockout (C5aR1KO), Arctic (ARC) and Arctic C5aR1 knockout (ARCKO) mice at 2, 5, 7 and 10-11 month. Duplicates were sequenced for each genotype on Illumina HiSeq 2500 platform.
Prevention of C5aR1 signaling delays microglial inflammatory polarization, favors clearance pathways and suppresses cognitive loss.
Age, Specimen part, Subject
View SamplesObjectives: We studied the signal transduction of atrial structural remodelling that contributes to
Rac1-induced connective tissue growth factor regulates connexin 43 and N-cadherin expression in atrial fibrillation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of a novel PPARβ/δ/miR-21-3p axis in UV-induced skin inflammation.
Specimen part, Cell line
View SamplesAlthough excessive exposure to UV is widely recognized as a major factor leading to skin perturbations and cancer, the complex mechanisms underlying inflammatory skin disorders resulting from UV exposure remain incompletely characterized. The nuclear hormone receptor PPAR/ is known to control cutaneous repair and UV-induced cancer development. Here, we describe a novel PPAR/-dependent molecular cascade involving TGF-1 and miR-21-3p, which is activated in the epidermis in response to UV exposure. We establish that the passenger miRNA miR-21-3p, that we identify as a novel UV-induced miRNA in the epidermis, plays a pro-inflammatory function in keratinocytes, and that its high level of expression in human skin is associated with psoriasis and squamous cell carcinomas. Finally, we provide evidence that inhibition of miR-21-3p reduces UV-induced cutaneous inflammation in ex vivo human skin biopsies, thereby underlining the clinical relevance of miRNA-based topical therapies for cutaneous disorders.
Identification of a novel PPARβ/δ/miR-21-3p axis in UV-induced skin inflammation.
Specimen part
View SamplesAlthough excessive exposure to UV is widely recognized as a major factor leading to skin perturbations and cancer, the complex mechanisms underlying inflammatory skin disorders resulting from UV exposure remain incompletely characterized. The nuclear hormone receptor PPAR/ is known to control cutaneous repair and UV-induced cancer development. Here, we describe a novel PPAR/-dependent molecular cascade involving TGF-1 and miR-21-3p, which is activated in the epidermis in response to UV exposure. We establish that the passenger miRNA miR-21-3p, that we identify as a novel UV-induced miRNA in the epidermis, plays a pro-inflammatory function in keratinocytes, and that its high level of expression in human skin is associated with psoriasis and squamous cell carcinomas. Finally, we provide evidence that inhibition of miR-21-3p reduces UV-induced cutaneous inflammation in ex vivo human skin biopsies, thereby underlining the clinical relevance of miRNA-based topical therapies for cutaneous disorders.
Identification of a novel PPARβ/δ/miR-21-3p axis in UV-induced skin inflammation.
Cell line
View SamplesBackground: We got interested whether genes of airway basal cells are enriched in COPD.
BAL Cell Gene Expression Is Indicative of Outcome and Airway Basal Cell Involvement in Idiopathic Pulmonary Fibrosis.
Specimen part, Disease
View SamplesBackground: We got interested whether genes of airway basal cells are enriched in sarcoidosis.
BAL Cell Gene Expression Is Indicative of Outcome and Airway Basal Cell Involvement in Idiopathic Pulmonary Fibrosis.
Specimen part, Disease
View Samples