Project description:This SuperSeries is composed of the following subset Series: GSE32278: Genome-wide analysis of lupus immune complex stimulation of purified CD14+ monocytes and how this response is regulated by C1q GSE32279: Genome-wide analysis of lupus immune complex stimulation of peripheral blood mononuclear cells and how this is regulated by C1q Refer to individual Series
Project description:Systemic sclerosis (SSc) is an autoimmune disease and several distinct autoantibodies have been described in SSc patients, many correlating with specific clinical presentation. Numerous studies have documented the presence of immune complexes (IC) in sera, lungs and BAL of SSc patients, potentially implicating them in the pathogenesis. Monocyte/macrophage activation also have been observed in fibrotic SSc skin and lung tissue. While the upstream activators remain unknown, it is plausible that IC are amongst the key triggers in activating monocytes and sustaining the chronic inflammation and fibrosis in SSc tissue. To test this hypothesis and find the specific downstream genes regulated by IC, we compare the gene expressions of the monocytes stimulated by control medium, LPS and IC using RNA seq. OPN was one of these IC regulated genes. Our paper further suggested that circulating OPN levels serve as a systemic proxy for IC driven profibrotic macrophage activity, highlighting its potential as a promising biomarker in SSc-ILD.
Project description:The goal of this study was to determine what genes are up- and down-regulated in response to lupus immune complexes in purified CD14+ monocyte stimulations. Our results have shown that novel genes are induced by immune complexes but the response is less robust when using purified monocytes versus total PBMCs Total RNA was isolated from CD14+ monocytes from 2 donors after 5 hours with the following conditions: 1) Unstimulated, 2) Lupus immune complex alone, 3) Lupus immune complex + C1q, 4) C1q alone
Project description:To evaluate gene expression in human peripheral blood derived monocytes over the course of an LPS stimulation time-series. Keywords: time course
Project description:We wished to investigate differential effects of stimulation with immune complex on colonic macrophages taken from mice which were either healthy or had DSS induced colitis.
Project description:Exposure of human monocytes to lipopolysaccharide (LPS) or other pathogen-associated molecular pattern (PAMPs) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance (ET). The tolerant state of monocytes is accompanied by cell surface and other glycoprotein expression changes induced by the activation of Toll-like receptors (TLRs). In this study, we aimed to characterize the cellular state of human monocytes stimulated with Gram-positive Staphylococcus aureus and TLR2 ligands. We analyzed gene expression changes induced by S. aureus after 2 and 24 hours by amplicon sequencing (RNA-AmpliSeq) and compared the pro-inflammatory response after 2 hours of stimulation to the to the response in re-stimulation experiments after the first stimulus. In parallel, glycoprotein expression changes in human monocytes after 24 hours of S. aureus stimulation were analyzed by proteomics and compared to stimulation experiments with TLR2 ligands Malp-2 and Pam3Cys and TLR4 ligand LPS. The results demonstrate that monocytes stimulated with S. aureus and TLR ligands entered the tolerant cell state after activation. Compared to TLR agonist mediated activation and tolerization of monocytes, glycoprotein expression changes induced by S. aureus stimulation revealed significant differences in receptor expression profiles. We report a glycoprotein expression profile characteristic for PAMP and S. aureus tolerized human monocytes. Finally, we analyzed peripheral blood monocytes of patients with S. aureus bloodstream infection for inflammatory responses in vitro and for their glycoprotein expression profiles. RNA-AmpliSeq data from patient-derived monocytes demonstrated that the cells were pro-inflammatory responsive to S. aureus stimulation and expressed higher level of CD44 mRNA, while other markers of the tolerant cell state were not detected.
Project description:As innate immune cells, monocytes play a central role in antifungal immunity. Using proteome studies in primary human monocytes, which were stimulated by Candida albicans (yeast) in vitro. Here we describe the changes of proteins in monocytes and demonstrate that in the early stage of infection, the differences of innate immune response triggered by C. albicans over time.
Project description:To evaluate gene expression in human peripheral blood derived monocytes over the course of an LPS stimulation time-series. Experiment Overall Design: Blood samples from three individuals, each sample split into separate culture for each timepoint (0, 2, 4, 8, and 24 hours). RNA prepared from all, and analyzed with Bioanalyzer. Two best RNA samples from each timepoint analyzed by hybridization to a chip.