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Expression profiles of human interferon‐alpha and interferon‐lambda subtypes are ligand‐ and cell‐dependent
Author(s) -
Hillyer Philippa,
Mane Viraj P,
Schramm Lynnsie M,
Puig Montserrat,
Verthelyi Daniela,
Chen Aaron,
Zhao Zeng,
Navarro Maria B,
Kirschman Kevin D,
Bykadi Srikant,
Jubin Ronald G,
Rabin Ronald L
Publication year - 2012
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2011.109
Subject(s) - interferon , biology , oligonucleotide , alpha interferon , peripheral blood mononuclear cell , cpg oligodeoxynucleotide , microbiology and biotechnology , cell type , dendritic cell , interferon type i , innate immune system , cpg site , immunology , cell , gene , immune system , gene expression , in vitro , genetics , dna methylation
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.