Systematic name M2979
Brief description Genes down-regulated in peripheral blood mononclear cells (PBMC) from multiple sclerosis (MS) patient: untreated versus IFNB1 [GeneID=3456].
Full description or abstract IFN?, an effective therapy against relapsing-remitting (RR) multiple sclerosis (MS) is naturally secreted during the innate immune response against viral pathogens. The objective of this study was to characterize the immunomodulatory mechanisms of IFN? targeting innate immune response and their effects on DC-mediated regulation of T-cell differentiation. We found that IFN??1a in-vitro treatment of human monocyte-derived dendritic cells (DCs) induced the expression of TLR7 and the members of its downstream signaling pathway, including myeloid differentiation factor 88 (MyD88), IL-1R-associated kinase (IRAK)4, and TNF receptor-associated factor (TRAF)6, while it inhibited the expression of IL-1R. Using siRNA TLR7 gene silencing, we confirmed that IFN?-1a-induced changes in MyD88, IRAK4 and IL-1R expression were dependent on TLR7. TLR7 expression was also necessary for the IFN?-1a-induced inhibition of IL-1? and IL-23, and the induction of IL-27 secretion by DCs. Supernatant (SN) transfer experiments confirmed that IFN?-1a-induced changes in DCs? cytokine secretion inhibit Th17 cell differentiation as evidenced by the inhibition of retinoic acid-related orphan nuclear hormone receptor C (RORC) and IL-17A gene expression and IL-17A secretion. Our study has identified a novel therapeutic mechanism of IFN??1a, that selectively targets the autoimmune response in MS.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 19265172   Authors: Zhang X,Jin J,Tang Y,Speer D,Sujkowska D,Markovic-Plese S
Exact source GSE14386_2514_200_DN
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Source species Homo sapiens
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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