Project description:We compared gene expression profile between healthy-donor peripheral monocytes and glioblastoma-patient peripheral monocytes as well as glioblastoma-patient peripheral monocytes with matched tumor-infiltrating myeloid cells.
Project description:The project was designed to figure out the role of microglia in brain inflammation (EAE model). The first step was to find genes/pathways that are upregulated in the microglia during EAE progress but absent in the infiltrating monocytes. These genes/pathways may provide clues for studying the unique function of microglia in the brain inflammation that is disctinct from the infiltrating monocytes.
Project description:MicroRNAs (miRNAs) are non-coding molecules involved in post-transcriptional gene regulation that have been shown to modulate tumor cell proliferation and apoptosis and to act as oncogenes or tumor-suppressor genes. Although miRNAs have been linked to tumor progression, the connection between tumor-mediated immune modulation and miRNAs has yet to be explored. Specifically, how the miRNA dysregulation affects the monocyte-derived glioblastoma-infiltrating macrophages, the most abundant immune cell population within the glioblastoma microenvironment, and their immune suppressive properties has not been evaluated to date. Here we managed to purify the glioblastoma-infiltrating macrophages from the tumor microenvironment and compared their miRNA expression profile with the matched peripheral monocytes from the peripheral blood of the same GBM patient as well as with healthy donors. Of note, several most down-regulated miRNA candidates revealed in this study, including miR-142-3p, were also known for their role in mediating tumor-associated immunosuppression. These results suggest a novel approach to identify miRNA immune therapeutics using a two-step process: 1) screen miRNA expression from tumor-associated immune cells relative to normal immune cell, and 2) select and prioritize potential candidates on the basis of binding to immunosuppressive pathways or mechanisms. In the study presented here, 12 samples, including peripheral monocyte samples from 4 healthy donors, peripheral monocytes from 4 GBM patients and matched tumor-infiltrating macrophages extracted from the glioblastoma microenvironment, were used to acquire the miRNA expression profiles of 1732 unique mature miRNA sequences via the Phalanx Human miRNA OneArray Microarray v3 Platform.
Project description:Immunometabolism is one of the recent targets to modify the immunological resposes as well as to inhibit the autoimmunity. We used microarrays to detail the global programme of gene expression underlying immumetabolism and identified distinct classes of up-regulated genes during this process.
Project description:COVID-19 patients are generally asymptomatic during initial SARS-CoV-2 replication, but may suffer severe immunopathology after the virus has receded and blood monocytes have infiltrated the airways. In the bronchoalveolar lavage fluid from patients with severe COVID-19, lung-infiltrating monocytes expressed high mRNA levels encoding inflammatory mediators, including CXCL8and IL-1ß, and contained SARS-CoV-2transcripts. To study this process in more depth, we developed a novel organotypic model whereby primary human blood monocytes are transmigrated across a differentiated human lung epithelium infected by SARS-CoV-2. Infiltrating monocytes acquiredSARS-CoV-2 from the epithelium and upregulated expression and secretion of inflammatory mediators includingCXCL8 and IL-1ß, mirroring in vivo data. The JAK1/2inhibitor baricitinib gained emergency use authorization by the FDA for the treatment of COVID-19 originally in combination with the antiviral remdesivir, and recently as a stand-alone treatment. To explore the mechanisms by which baricitinib alone or in combination with remdesivir may result in more favorable disease outcomes, we leveraged this model to characterize viral burden, gene expression and inflammatory mediator secretion by lung epithelial cells and infiltrating monocytes. As expected, remdesivir decreased viral burden in both the epithelium and monocytes, while baricitinib enhanced antiviral signaling and decreased specific inflammatory mediators in monocytes. Combined use of baricitinib and remdesivir enhanced the rate of virus clearance from SARS-CoV-2-positivemonocytes. Taken together, baricitinib enhances the antiviral state of monocytes infiltrating the COVID-19 lung, while decreasing the expression of inflammatory mediators, thus limiting the likelihood of a cytokine storm and ensuing acute respiratory distress syndrome (ARDS).
Project description:To study the molecular mechanism of tumor associated macrophages (TAMs), the RNA of infiltrating monocytes derived from in vitro liver cancer spheroid model were performed. The results indicated that the cholesterol metabolism-related genes enriched in the infiltrating monocytes, which presented the M2-like TAM phenotypes.