title: Expression profiles of human interferon-alpha and interferon-lambda subtypes are ligand- and cell-dependent.
abstract: Recent genome-wide association studies suggest distinct roles for 12 human interferon-alpha (IFN-α) and 3 IFN-λ subtypes that may be elucidated by defining the expression patterns of these sets of genes. To overcome the impediment of high homology among each of the sets, we designed a quantitative real-time PCR assay that incorporates the use of molecular beacon and locked nucleic acid (LNA) probes, and in some instances, LNA oligonucleotide inhibitors. We then measured IFN subtype expression by human peripheral blood mononuclear cells and by purified monocytes, myeloid dendritic cells (mDC), plasmacytoid dendritic cells (pDC), and monocyte-derived macrophages (MDM), and -dendritic cells (MDDC) in response to poly I:C, lipopolysaccharide (LPS), imiquimod and CpG oligonucleotides. We found that in response to poly I:C and LPS, monocytes, MDM and MDDC express a subtype pattern restricted primarily to IFN-β and IFN-λ1. In addition, while CpG elicited expression of all type I IFN subtypes by pDC, imiquimod did not. Furthermore, MDM and mDC highly express IFN-λ, and the subtypes of IFN-λ are expressed hierarchically in the order IFN-λ1 followed by IFN-λ2, and then IFN-λ3. These data support a model of coordinated cell- and ligand-specific expression of types I and III IFN. Defining IFN subtype expression profiles in a variety of contexts may elucidate specific roles for IFN subtypes as protective, therapeutic or pathogenic mediators.
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892-4555, USA.
authors.forename: Philippa
authors.initials: P
authors.lastname: Hillyer
authors.forename: Viraj P
authors.initials: VP
authors.lastname: Mane
authors.forename: Lynnsie M
authors.initials: LM
authors.lastname: Schramm
authors.forename: Montserrat
authors.initials: M
authors.lastname: Puig
authors.forename: Daniela
authors.initials: D
authors.lastname: Verthelyi
authors.forename: Aaron
authors.initials: A
authors.lastname: Chen
authors.forename: Zeng
authors.initials: Z
authors.lastname: Zhao
authors.forename: Maria B
authors.initials: MB
authors.lastname: Navarro
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Kirschman
authors.forename: Srikant
authors.initials: S
authors.lastname: Bykadi
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Jubin
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Rabin
mesh_terms: D000818:Animals; D015342:DNA Probes / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics* / Q000378:metabolism; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D051193:Toll-Like Receptors / Q000378:metabolism; D000095022:Interferon Lambda
chemical_list: D015342:DNA Probes; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D008024:Ligands; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D011070:Poly I-C; D012333:RNA, Messenger; D051193:Toll-Like Receptors; C408982:CPG-oligonucleotide; C554156:IFNA1 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda