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Publication : Type I interferon negatively controls plasmacytoid dendritic cell numbers in vivo.

First Author  Swiecki M Year  2011
Journal  J Exp Med Volume  208
Issue  12 Pages  2367-74
PubMed ID  22084408 Mgi Jnum  J:178613
Mgi Id  MGI:5299366 Doi  10.1084/jem.20110654
Citation  Swiecki M, et al. (2011) Type I interferon negatively controls plasmacytoid dendritic cell numbers in vivo. J Exp Med 208(12):2367-74
abstractText  Plasmacytoid dendritic cells (pDCs) specialize in the secretion of type I interferons (IFN-I) and thus are considered critical mediators of antiviral responses. We recently reported that pDCs have a very early but limited and transient capacity to curtail viral infections. Additionally, pDC numbers are not sustained in human infections caused by Hepatitis B or C viruses (HBV and HCV) and HIV. Thus, the numbers and/or function of pDCs appear to be regulated during the course of viral infection. In this study, we show that splenic pDCs are reduced in vivo during several systemic viral infections and after administration of synthetic toll-like receptor ligands. We demonstrate that IFN-I, regardless of the source, contributes to this decline and mediates pDC death via the intrinsic apoptosis pathway. These findings demonstrate a feedback control mechanism by which IFN-I modulates pDC numbers, thus fine-tuning systemic IFN-I response to viruses. IFN-I-mediated control of pDCs may explain the loss of pDCs during human infections caused by HBV, HCV, or HIV and has important therapeutic implications for settings in which IFN-I is used to treat infections and autoimmune diseases.
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