Premium
IRF ‐5 and NF ‐κ B p50 co‐regulate IFN ‐β and IL ‐6 expression in TLR 9‐stimulated human plasmacytoid dendritic cells
Author(s) -
Steinhagen Folkert,
McFarland Adelle P.,
Rodriguez Luis G.,
Tewary Poonam,
Jarret Abigail,
Savan Ram,
Klinman Dennis M.
Publication year - 2013
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201242792
Subject(s) - tlr9 , biology , innate immune system , cpg oligodeoxynucleotide , toll like receptor 9 , cpg site , immune system , p50 , plasmacytoid dendritic cell , microbiology and biotechnology , dendritic cell , interferon , immunology , gene expression , gene , transcription factor , dna methylation , genetics
Synthetic oligonucleotides ( ODN ) expressing C p G motifs mimic the ability of bacterial DNA to trigger the innate immune system via TLR 9. Plasmacytoid dendritic cells (p DC s) make a critical contribution to the ensuing immune response. This work examines the induction of antiviral ( IFN ‐β) and pro‐inflammatory ( IL ‐6) cytokines by C p G ‐stimulated human p DC s and the human CAL ‐1 p DC cell line. Results show that interferon regulatory factor‐5 ( IRF ‐5) and NF ‐κ B p50 are key co‐regulators of IFN ‐β and IL ‐6 expression following TLR 9‐mediated activation of human p DC s. The nuclear accumulation of IRF ‐1 was also observed, but this was a late event that was dependant on type 1 IFN and unrelated to the initiation of gene expression. IRF ‐8 was identified as a novel negative regulator of gene activation in C p G ‐stimulated p DC s. As variants of IRF ‐5 and IRF ‐8 were recently found to correlate with susceptibility to certain autoimmune diseases, these findings are relevant to our understanding of the pharmacologic effects of “ K ” ODN and the role of TLR 9 ligation under physiologic, pathologic, and therapeutic conditions.