Comparative analysis of IRF and IFN-alpha expression in human plasmacytoid and monocyte-derived dendritic cells

Journal of Leukocyte Biology

Jihong Dai²  Alexander Izaguirre⁴  Patricia Fitzgerald-Bocarsly³  Paula M. Pitha¹  Sheela Amrute⁵  Wen-Shuz Yeow²  Eugene Chung⁴  Nicholas Megjugorac⁴  Betsy J. Barnes²  Di Feng⁴ 

[1] The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231; and the The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231; and the The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231; and the;UMDNJ-New Jersey Medical School, UMDNJ–Graduate School for Biomedical Sciences, Newark, NJ 07103; Cancer Institute of New Jersey UMDNJ-New Jersey Medical School, UMDNJ-New Jersey Medical School, UMDNJ–Graduate School for Biomedical Sciences, Newark, NJ 07103; Cancer Institute of New Jersey UMDNJ–Graduate School for Biomedical Sciences, Newark, NJ 07103; UMDNJ-New Jersey Medical School, UMDNJ–Graduate School for Biomedical Sciences, Newark, NJ 07103; Cancer Institute of New Jersey Cancer Institute of New Jersey UMDNJ-New Jersey Medical School, UMDNJ–Graduate School for Biomedical Sciences, Newark, NJ 07103; Cancer Institute of New JerseyUMDNJ-New Jersey Medical School, UMDNJ–Graduate School for Biomedical Sciences, Newark, NJ 07103; UMDNJ-New Jersey Medical School, UMDNJ-New Jersey Medical School, UMDNJ–Graduate School for Biomedical Sciences, Newark, NJ 07103; UMDNJ–Graduate School for Biomedical Sciences, Newark, NJ 07103; UMDNJ-New Jersey Medical School, UMDNJ–Graduate School for Biomedical Sciences, Newark, NJ 07103;;UMDNJ-New Jersey Medical School, UMDNJ-New Jersey Medical School, UMDNJ-New Jersey Medical School,

关键词: IRF-7;    interferon producing cells;    PDC;   

DOI  :  10.1189/jlb.0603255

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Plasmacytoid dendritic cells (PDC) produce high levels of type I IFN upon stimulation with viruses, while monocytes and monocyte-derived dendritic cells (MDDC) produce significantly lower levels. To find what determines the high production of type I IFN in PDC, we examined the relative levels of IRF transcription factors, some of which play critical roles in the induction of IFN. Furthermore, to determine whether the differences could result from expression of distinct IFNA subtypes, the profile of IFNA genes expressed was examined. PDC responded equally well to stimulation with HSV-1 and Sendai virus (SV) by producing high levels of type I IFN, whereas the MDDC and monocyte response to SV were lower, and neither responded well to HSV-1. All three populations constitutively expressed most of the IRF genes. However, real-time RT-PCR demonstrated increased levels of IRF-7 transcripts in PDC compared with monocytes. As determined by intracellular flow cytometry, the PDC constitutively expressed significantly higher levels of IRF-7 protein than the other populations while IRF-3 levels were similar among populations. Analysis of the profile of IFNA genes expressed in virus-stimulated PDC, monocytes and MDDC demonstrated that each population expressed IFNA1 as the major subtype but that the range of the subtypes expressed in PDC was broader, with some donor and stimulus-dependent variability. We conclude that PDC but not MDDC are uniquely preprogrammed to respond rapidly and effectively to a range of viral pathogens with high levels of IFN-α production due to the high levels of constitutively expressed IRF-7.

【 授权许可】

Unknown