CTD-ILD BALF and blood scRNA-seq data
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ABSTRACT:
PROVIDER: EGAS00001007539 | EGA |
REPOSITORIES: EGA
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Project description:To clarify the profile of in BALF exosome collected from mice infected with influenza virus, we infected 100000 pfu of A/Puerto Rico/8/1934 (PR8) strain. BALF was collected at 24, 48, and 72 hour post infection (hpi). For comparison of the profile of the miRNA in BALF exosome induced by innate immune response, we also intranasally inoculated mice with 50 μg of poly(I:C) and collected BALF at 72 hour post inoculation. We found that some miRNAs were common to both influenza virus infectiona and poly(I:C) inoculation, suggesting that exosomal miRNAs in BALF may function in the innate immune response to virus infection.
2018-06-08 | GSE107107 | GEO
Project description:This study investigated whether mitochondria-targeted peptide SS-31 played a protective role in cigarette smoke (CS)-induced airway inflammation and oxidative stress in mice. Mice were exposed to CS for 4 weeks to establish a CS-induced airway inflammation model, then treated with SS-31. Pathological changes and oxidative stress in lung tissue, inflammatory cell counts and pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were examined. RNA sequencing from lung tissue and western blotting were conducted to investigate mechanisms. SS-31 attenuated CS-induced inflammatory injury of the airway. Numbers of total cells, neutrophils, and macrophages and levels of tumor necrosis factor α, interleukin 6, and matrix metallopeptidase 9 in BALF were markedly reduced by SS-31. SS-31 attenuated CS-induced oxidative stress by decresing malondialdehyde and myeloperoxidase levels, and increasing superoxide dismutase activity. It also reversed the expression of mitochondrial fission protein and optic atrophy 1 protein, and reduced cytochrome c release into the cytosol. RNA sequencing revealed that SS-31 changed CS-induced expression profiles and enriched MAPK pathway, western blotting confirmed that SS-31 inhibited the CS-activated MAPK pathway. SS-31 alleviates CS-induced airway inflammation and oxidative stress, possibly via the regulation of mitochondrial function and MAKP pathway, SS-31 may be a novel drug for CS-induced airway disorders.
2020-12-25 | GSE163835 | GEO
Project description:Background. The Dahl salt-sensitive (SS) rat is an established model of salt-sensitive hypertension and renal damage. Recently, sodium-independent dietary effects were shown to be important in the development of the SS hypertensive phenotype. Compared to Dahl SS/JrHsdMcwi (SS/MCW) rats fed a purified diet (AIN-76A), grain-fed Dahl SS/JrHsdMcwiCrl rats (SS/CRL; Teklad 5L2F) were less susceptible to salt-induced hypertension and renal damage. Methods. With the known role of the immune system in hypertension, the present study characterized the immune cells infiltrating SS/MCW and SS/CRL kidneys. To further identify distinct molecular pathways between SS/MCW and SS/CRL, transcriptomic analysis was performed via RNA sequencing in T-cells isolated from the blood and kidneys of low and high salt-fed rats. Results. Following a 3-week high salt (4.0% NaCl) challenge, SS/CRL rats were protected from salt-induced hypertension (116.5±1.2 vs 141.9±14.4 mmHg) and albuminuria (21.7±3.5 vs 162.9±22.2 mg/day) compared to SS/MCW. Additionally, the absolute number of immune cells infiltrating the kidney was significantly reduced in SS/CRL. RNA-seq revealed >50% of all annotated genes in the entire transcriptome to be significantly differentially expressed in T-cells isolated from blood versus kidney. Pathway analysis of significant differentially expressed genes between SS/MCW and SS/CRL renal and circulating T-cells demonstrated salt-induced changes in genes related to inflammation in SS/MCW compared to metabolism-related pathways in SS/CRL. Conclusions. These functional and transcriptomic T-cell differences between SS/MCW and SS/CRL show that sodium-independent dietary effects may influence the immune response and infiltration of immune cells into the kidney, ultimately impacting susceptibility to salt-induced hypertension and renal damage.
2019-08-26 | GSE127000 | GEO
Project description:Bronchoalveolar lavage is commonly performed to examine inflammation and responsible pathogens in lung diseases, and its findings may be used to assess the immune profile of the lung tumor microenvironment (TME). To investigate whether analyses of bronchoalveolar lavage fluid (BALF) can help identify non-small cell lung cancer (NSCLC) patients who respond to immune checkpoint inhibitors (ICIs), BALF and blood were prospectively collected before initiating nivolumab. The secreted molecules, microbiome, and cellular profiles based on BALF and blood analysis were compared regarding therapeutic effect in 12 patients. Compared to non-responders, responders showed significantly higher CXCL9 levels and greater diversity in the lung microbiome profile in BALF, and greater frequency of CD56+ subset in blood T cells, whereas no significant difference was found in PD-L1 expression of tumor cells. Antibiotic treatment in a preclinical lung cancer model significantly decreased CXCL9 in the lung TME, resulting in reduced sensitivity to nivolumab, which was reversed by CXCL9 induction in tumor cells. Thus, CXCL9 and the microbiome in the lung TME might be associated with each other, and their balance could contribute to nivolumab sensitivity in NSCLC patients. BALF analysis can help predict the efficacy of ICIs when performed along with currently approved examinations.
2022-04-07 | GSE193049 | GEO
Project description:The signal transducer and activator of transcription 6 (STAT-6) is a critical up-stream mediator of IL-13 and IL-4 signaling and is constitutively activated in malignant lymphocytes from Sezary syndrome (SS) and mycosis fungoides (MF), the most common subtypes of cutaneous T-cell lymphomas. By combining genome-wide expression profiling with pharmacological STAT-6 inhibition, we have identified the genes regulated by STAT-6 in MF/SS tumors. We found that STAT-6 regulates several common pathways in MF/SS malignant lymphocytes that are associated with control of cell cycle progression and genomic stability as well as production of Th2 cytokines. Using ex vivo skin explants from cutaneous MF tumors as well as Sezary cells derived from the blood of SS patients, we demonstrated that inhibition of STAT-6 activation down-regulates cytokine production and induces cell cycle arrest in MF/SS malignant lymphocytes, inhibiting their proliferation but not their survival. Furthermore, we show that STAT-6 promotes the pro-tumoral M2-like phenotype of tumor-associated macrophages in the tumor microenvironment of advanced-stage MF by up-regulating the expression of genes associated with immunosuppression, chemotaxis, and tumor matrix remodeling. Thus, we show STAT-6 to be a major factor in the pathogenesis and progression of MF/SS, promoting proliferation and invasion of the malignant lymphocytes while inducing a progressive depression of the anti-tumor immune response. Together, our results provide new insights into disease pathogenesis and offer new prospective targets for therapeutic intervention.
2020-10-22 | GSE147944 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is ranked the third leading cause of death worldwide and hence constitutes a significant burden, both medically and financially. To date, the cellular mechanism underlying COPD is poorly understood and thus no effective therapy is currently available. To broaden the current knowledge of the immune landscape in the alveolar space, we performed scRNA-Seq of CD45-enriched bronchoalveolar lavage fluid (BALF) cells and isolated blood leukocytes obtained from COPD patients and healthy controls using both the Seq-Well and the Chromium (10x Genomics) technology.
| EGAS00001004369 | EGA
Project description:Cutaneous T-cell lymphomas are a heterogeneous group of neoplasms originating in the skin, with mycosis fungoides (MF) and Sézary syndrome (SS) representing the most common variants. The cellular origin of cutaneous lymphomas has remained controversial due to their immense phenotypic heterogeneity that obfuscates lineage reconstruction based on classical surface biomarkers. To overcome this heterogeneity and reconstruct the differentiation trajectory of malignant cells in MF and SS, T-cell receptor sequencing was performed in parallel with targeted transcriptomics at the single-cell resolution among cutaneous samples in MF and SS. Unsupervised lineage reconstruction showed that Sézary cells exist as a population of CD4+ T cells distinct from those in patch, plaque, and tumor MF. Further investigation of malignant cell heterogeneity in SS showed that Sézary cells phenotypically comprised at least three subsets based on differential proliferation potentials and expression of exhaustion markers. A Th1 polarized cell type, intermediate cell type, and exhausted Th2 polarized cell type were identified, with Th1 and Th2 polarized cells displaying divergent proliferation potentials. Collectively, these findings provide evidence to clarify the relationship between MF and SS, and reveal cell subsets in SS that suggest a possible mechanism for therapeutic resistance.
2022-12-31 | GSE192836 | GEO
Project description:Immune characteristics associated with Coronavirus Disease-2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid (BALF) immune cells from patients with varying severity of COVID-19 disease and from healthy subjects using single-cell RNA-sequencing. Proinflammatory monocyte-derived macrophages were abundant in the BALF from severe COVID-9 patients. Moderate cases were characterized by the presence of highly clonally expanded tissue-resident CD8+ T cells. This atlas of the bronchoalveolar immune-microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19.
2020-04-22 | GSE145926 | GEO
Project description:Endothelial cells (ECs) are constantly submitted in vivo to hemodynamical forces derived from the blood circulation, including shear stress (SS). EC are able to detect SS and consequently adapt their phenotype, thus affecting many endothelial functions. If a plethora of shear stress-regulated molecular networks have been described in peripheral EC, less is known about the molecular responses of microvascular brain ECs which constitute the blood-brain barrier (BBB). In this work, we investigated the response of human cerebral microvascular ECs to laminar physiological shear stress using the well characterized hCMEC/D3 cell line. Interestingly, we showed that hCMEC/D3 cells responded to shear stress by aligning perpendicularly to the flow direction, contrary to peripheral endothelial cells which aligned in the flow direction. Whole proteomic profiles were compared between hCMEC/D3 cells cultured either in static condition or under 5 or 10 dyn.cm-2 SS for three days. 3592 proteins were identified and expression levels were significantly affected for 3% of them upon both SS conditions. Pathway analyses were performed which revealed that most proteins overexpressed by SS refer to the antioxidant defense, probably mediated by activation of the NRF2 transcriptional factor. Regarding down-regulated proteins, most of them participate to the pro-inflammatory response, cell motility and proliferation. These findings confirm the induction of EC quiescence by laminar physiological SS and reveal a strong neuroprotective effect of SS on hCMEC/D3 cells, suggesting a similar effect on the BBB. Our results also showed that SS did not significantly increase expression levels nor did it affect the localization of junctional proteins or the functional activity of several ABC transporters (P-glycoprotein and MRPs). This work provides new insights on the response of microvascular brain EC to SS and on the importance of SS for optimizing in vitro BBB models.
2022-08-12 | PXD030493 | Pride