PMID- 17702615 OWN - NLM STAT- MEDLINE DCOM- 20071113 LR - 20240109 IS - 1074-7613 (Print) IS - 1097-4180 (Electronic) IS - 1074-7613 (Linking) VI - 27 IP - 2 DP - 2007 Aug TI - The feedback phase of type I interferon induction in dendritic cells requires interferon regulatory factor 8. PG - 228-39 AB - Dendritic cells (DCs) produce type I interferons (IFNs) in greater amounts than other cells, but the mechanisms remain elusive. Here we studied the role of a transcription factor, IRF8, in DC induction of type I IFNs. Upon newcastle disease virus (NDV) infection, bone marrow-derived plasmacytoid and conventional DCs induced IFN transcripts, exhibiting two-phase kinetics. The second, amplifying phase represented an IFN feedback response that accounted for much of IFN protein production. Induction of second phase transcription required IRF8. Mouse cytomegalovirus (MCMV) and Toll-like receptor-mediated IFN induction in DCs also required IRF8. Chromatin immunoprecipitation analysis showed that IRF7, IRF8, and RNA polymerase II were recruited to the IFN promoters upon stimulation. Moreover, sustained RNA polymerase II recruitment to the promoters critically depended on IRF8. Together, these data indicate that IRF8 magnifies the second phase of IFN transcription in DCs by prolonging binding of basic transcription machinery to the IFN promoters, thereby playing a role in innate immunity. FAU - Tailor, Prafullakumar AU - Tailor P AD - Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Tamura, Tomohiko AU - Tamura T FAU - Kong, Hee Jeong AU - Kong HJ FAU - Kubota, Toru AU - Kubota T FAU - Kubota, Mayumi AU - Kubota M FAU - Borghi, Paola AU - Borghi P FAU - Gabriele, Lucia AU - Gabriele L FAU - Ozato, Keiko AU - Ozato K LA - eng GR - Z01 HD001310-21/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural DEP - 20070816 PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Interferon Regulatory Factor-7) RN - 0 (Interferon Regulatory Factors) RN - 0 (Interferon Type I) RN - 0 (Irf7 protein, mouse) RN - 0 (interferon regulatory factor-8) RN - EC 2.7.7.- (RNA Polymerase II) SB - IM MH - Animals MH - Chromatin Immunoprecipitation MH - Dendritic Cells/*immunology MH - Feedback, Physiological MH - Fibroblasts/immunology MH - *Gene Expression Regulation MH - Interferon Regulatory Factor-7/metabolism MH - Interferon Regulatory Factors/genetics/*metabolism MH - Interferon Type I/*genetics MH - Mice MH - Mice, Mutant Strains MH - Promoter Regions, Genetic MH - RNA Polymerase II/metabolism PMC - PMC2768351 MID - NIHMS30684 EDAT- 2007/08/19 09:00 MHDA- 2007/11/14 09:00 PMCR- 2009/10/27 CRDT- 2007/08/19 09:00 PHST- 2006/09/19 00:00 [received] PHST- 2007/04/03 00:00 [revised] PHST- 2007/06/11 00:00 [accepted] PHST- 2007/08/19 09:00 [pubmed] PHST- 2007/11/14 09:00 [medline] PHST- 2007/08/19 09:00 [entrez] PHST- 2009/10/27 00:00 [pmc-release] AID - S1074-7613(07)00368-8 [pii] AID - 10.1016/j.immuni.2007.06.009 [doi] PST - ppublish SO - Immunity. 2007 Aug;27(2):228-39. doi: 10.1016/j.immuni.2007.06.009. Epub 2007 Aug 16.