Project description:The goal of the experiment is to assess the effect of GLPG2534 and dexamethasone in the MC903 mouse model for atopic dermatitis in a therapeutic setting.
Project description:To investigate the mechanisms by which C/EBPa drives basophil differentiation and maintains basophil identity, we examined whether or not C/EBPa promotes basophil molecular programming and simultaneously represses mast cell molecular programming. We performed genome-wide gene expression profiling on basophils and mast cells and found that 6798 genes were shared by mast cells and basophils; 2033 genes were expressed 2-10 (log2 1-3.3)-fold higher in basophils (differentially expressed in basophils); and 413 genes were expressed greater than 10 (log2 3.3)-fold in basophils (highly expressed in basophils). On the other hand, we found 569 genes were expressed 2-10 (log2 -1 to -3.3) fold higher in mast cells and 171 genes were highly expressed in mast cells [greater than 10 fold (log2 -3.3)]. We treated purified basophils prepared from Cebpaf/f RosaYFP/creER mice and Cebpa+/+ RosaYFP/creER control mice with or without 4HT treatment for five days. Gene expression in the treated basophils was analyzed using microarray analysis. Overall, deletion of C/EBPa in basophils resulted in a reduction of mRNA expression for 248 genes and led to an increase in mRNA expression for 255 genes. The majority of the C/EBPa-regulated genes were either differentially or highly expressed in basophils or mast cells. In this study, we compared gene expression in basophils and mast cell and identified genes which specifically expressed in basophils and mast cells. By using Cebpa conditional knock out mice, we identified Cebpa regulated genes in basophils.
Project description:Basophils play crucial roles in type 2 immune responses, such as chronic allergic inflammation and protective immunity against parasites. However, the molecular mechanisms regulating basophil activation and effector molecule production remain poorly understood. To investigate the role of RNA-binding proteins (RBPs), we first analyzed the gene expression of CCCH zinc finger proteins in antigen/IgE-stimulated basophils. Among these proteins, we identified that Zfp36, encoding tristetraprolin (TTP), was the most significantly upregulated gene. Therefore, we focused on the functions of TTP in basophils. We generated TTP-KO mice using the CRISPR-Cas9 method and conducted bulk RNA-seq analysis of antigen/IgE-stimulated basophils from wild-type (WT) and TTP-knockout (TTP-KO) mice. TTP-KO basophils exhibited elevated mRNA expression of pro-inflammatory mediators, such as Il4, Il13, Areg, Ccl3, and Cxcl2, compared to WT basophils. These data suggest that TTP is a key regulator of basophil activation, controlling the mRNA expression of inflammatory mediators.
Project description:Challenge with ovalbumin antigen is a common model for asthma in mice. We sought to identify the gene expression differences in lung tissue in naïve and OVA-sensitized mice, in response to OVA challenge.
Project description:We report transcript abundance in skin, spinal_cord, and trigeminal ganglia from animals treated with MC903 to induce a mouse model of atopic dermatitis across different genotypes, time points, and treatments