title: Human pDCs display sex-specific differences in type I interferon subtypes and interferon α/β receptor expression.
abstract: The outcomes of many diseases differ between women and men, with women experiencing a higher incidence and more severe pathogenesis of autoimmune and some infectious diseases. It has been suggested that this is partially due to activation of plasmacytoid dendritic cells (pDCs), the main producers of interferon (IFN)-α, in response to toll-like receptor (TLR)7 stimulation. We investigated the induction of type I IFN (IFN-I) subtypes upon TLR7 stimulation on isolated pDCs. Our data revealed a sex-specific differential expression of IFN-Is, with pDCs from females showing a significantly higher mRNA expression of all 13 IFN-α subtypes. In addition, pDCs from females had higher levels of IFN-β mRNA after stimulation, indicating that sex differences in IFN-I production by pDCs were mediated by a signaling event upstream of the first loop of IFN-I mRNA transcription. Furthermore, the surface expression levels of the common IFN-α/β receptor subunit 2 were significantly higher on pDCs from females in comparison to males. These data indicate that higher IFN-α production is already established at the mRNA level and propose a contribution of higher IFN-α/β receptor 2 expression on pDCs to the immunological differences in IFN-I production observed between females and males.
authors.affiliation: Department of Virus Immunology, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Ziegler
authors.affiliation: Department of Virus Immunology, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.|Section Infectious Diseases, I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, and DZIF partner site (German Center for Infection Research), Hamburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Beisel
authors.affiliation: Institute for Virology University Hospital in Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Sutter
authors.affiliation: CIMI, Université Pierre et Marie Curie/INSERM U1135, Hospital Pitié Salpêtrière, Paris, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Griesbeck
authors.affiliation: Department of Virus Immunology, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Hildebrandt
authors.affiliation: Department of Virus Immunology, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Sven H
authors.initials: SH
authors.lastname: Hagen
authors.affiliation: Institute for Virology University Hospital in Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.affiliation: Department of Virus Immunology, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D007114:Immunization; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism*; D012723:Sex; D012727:Sex Characteristics; D015398:Signal Transduction; D051199:Toll-Like Receptor 7 / Q000276:immunology; D059467:Transcriptome
chemical_list: C508033:IFNAR2 protein, human; D007370:Interferon Type I; D012333:RNA, Messenger; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D053633:Receptor, Interferon alpha-beta
keywords: IFN-α; IFN-β; IFNAR; Sex differences pDCs; TLR7; Type I interferon