Gene expression in Mouse thrombomoudlin+ and thrombomodulin- dendritic cell. Mus musculus

Previously we had shown in a mouse model of bronchial asthma that thrombomodulin (TM; CD141; BDCA3) can convert immunogenic conventional dendritic cells into tolerogenic dendritic cells while inducing its own expression on the cell surface. Thrombomodulin+ dendritic cells are tolerogenic while thrombomodulin- dendritic cells are pro-inflammatory and immunogenic. Here we hypothesized that thrombomodulin treatment of dendritic cells would modulate inflammatory gene expression. Murine bone marrow derived dendritic cells were treated with soluble thrombomodulin and expression of surface markers was determined. Treatment with thrombomodulin reduces the expression of maturation markers and increases the expression of TM on the DC surface. Thrombomodulin treated and control dendritic cells were sorted into thrombomodulin+ and thrombomodulin- dendritic cells before their mRNA was analyzed by microarray. mRNAs encoding pro-inflammatory genes and dendritic cells maturation markers were reduced while cell cycle genes were increased in thrombomodulin-treated and thrombomodulin+ dendritic cells compared to control dendritic cells and thrombomodulin- dendritic cells. We compared the effects on global gene expression of treating dendritic cells with soulble thrombomodulin to no treatment, and dendritic cells separated into thrombomodulin+ and thrombomodulin- dendritic cell subsets. Overall design: In 4 independent experiments, RNA from mouse bone marrow derived dendritic cells were analyzed on Affymaetrix arrays to determine differences between thrombomodulin+ and thrombomodulin- dendritic cells and if treatment with soluble thrombomodulin altered gene expression.