title: Interferon-beta induces distinct gene expression response patterns in human monocytes versus T cells.
abstract: BACKGROUND
  Monocytes, which are key players in innate immunity, are outnumbered by neutrophils and lymphocytes among peripheral white blood cells. The cytokine interferon-β (IFN-β) is widely used as an immunomodulatory drug for multiple sclerosis and its functional pathways in peripheral blood mononuclear cells (PBMCs) have been previously described. The aim of the present study was to identify novel, cell-specific IFN-β functions and pathways in tumor necrosis factor (TNF)-α-activated monocytes that may have been missed in studies using PBMCs.
  
  
  RESULTS
  Whole genome gene expression profiles of human monocytes and T cells were compared following in vitro priming to TNF-α and overnight exposure to IFN-β. Statistical analyses of the gene expression data revealed a cell-type-specific change of 699 transcripts, 667 monocyte-specific transcripts, 21 T cell-specific transcripts and 11 transcripts with either a difference in the response direction or a difference in the magnitude of response. RT-PCR revealed a set of differentially expressed genes (DEGs), exhibiting responses to IFN-β that are modulated by TNF-α in monocytes, such as RIPK2 and CD83, but not in T cells or PBMCs. Known IFN-β promoter response elements, such as ISRE, were enriched in T cell DEGs but not in monocyte DEGs. The overall directionality of the gene expression regulation by IFN-β was different in T cells and monocytes, with up-regulation more prevalent in T cells, and a similar extent of up and down-regulation recorded in monocytes.
  
  
  CONCLUSIONS
  By focusing on the response of distinct cell types and by evaluating the combined effects of two cytokines with pro and anti-inflammatory activities, we were able to present two new findings First, new IFN-β response pathways and genes, some of which were monocytes specific; second, a cell-specific modulation of the IFN-β response transcriptome by TNF-α.
authors.affiliation: Division of Neuroimmunology and Multiple Sclerosis Center, Carmel Medical Center, Haifa, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Henig
authors.forename: Nili
authors.initials: N
authors.lastname: Avidan
authors.forename: Ilana
authors.initials: I
authors.lastname: Mandel
authors.forename: Elsebeth
authors.initials: E
authors.lastname: Staun-Ram
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Ginzburg
authors.forename: Tamar
authors.initials: T
authors.lastname: Paperna
authors.forename: Ron Y
authors.initials: RY
authors.lastname: Pinter
authors.forename: Ariel
authors.initials: A
authors.lastname: Miller
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D009928:Organ Specificity; D015203:Reproducibility of Results; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D051997:ADP-ribosyl Cyclase 1