IFN-g producing Th1 cells induce different transcriptional profiles in microglia and astrocytes

Autoreactive T cells that infiltrate into the central nervous system (CNS) are believed to have a significant role in mediating the pathology of neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis. Their interaction with microglia and astrocytes in the CNS is crucial for the regulation of the neuroinflammatory process. Our previous work demonstrated that effectors secreted by Th1 and Th17 cells have different capacities to influence the phenotype and function of the glial cells. We have shown that Th1 effectors altered the phenotype and function of both microglia and astrocytes whereas Th17 effectors induced direct effects only on astrocytes but not on microglia. Here we investigated if effector molecules associated with IFN-g producing Th1 cells induced different gene expression profiles in microglia and astrocytes. We performed a microarray analysis of RNA isolated from microglia and astrocytes treated with medium and Th1 culture supernatants and compared the gene expression data. By using the criteria of 2-fold change and a false discovery rate of 0.01 (corrected p-value < 0.01), we demonstrated that a total of 2106 and 1594 genes were differentially regulated microglia and astrocytes respectively in response to Th1-derived factors. We observed that Th1 associated effectors induce distinct transcriptional changes in microglia and astrocytes in addition to commonly regulated transcripts. These distinct transcriptional changes regulate distinct physiological functions and this knowledge can help in better understanding of T cell mediated neuropathologies. microarray analysis of RNA isolated from astrocytes treated with medium and Th1 culture supernatants Please note that in order to comparatively analyze this dataset with a previously generated, published microglia dataset [GSE45384], raw data from both studies were reprocessed and normalized together (as detailed in the sample data processing description) and the re-analyzed data is provided as a Series supplementary file: GSM1103441-GSM1103452_re-analyzed_GSE45384_matrix.txt