The host cell factor DDX3 mediates sex dimorphism in the IFNα response of plasmacytoid dendritic cells upon TLR activation
During the course of viral infections, IFN-I producing pDCs are fundamental in establishing antiviral defense. However, little is known about the molecular mechanisms by which biological sex contributes to differences in IFN-I production by pDCs. Here, we aimed to identify X-chromosome-encoded prote...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825001896 |
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| author | Sebastian Schloer Jana Hennesen Lena Rueschpler Mohamed Zamzamy Felix Flomm Wing Hang Ip Andrea Pirosu Thomas Dobner Marcus Altfeld |
| author_facet | Sebastian Schloer Jana Hennesen Lena Rueschpler Mohamed Zamzamy Felix Flomm Wing Hang Ip Andrea Pirosu Thomas Dobner Marcus Altfeld |
| author_sort | Sebastian Schloer |
| collection | DOAJ |
| description | During the course of viral infections, IFN-I producing pDCs are fundamental in establishing antiviral defense. However, little is known about the molecular mechanisms by which biological sex contributes to differences in IFN-I production by pDCs. Here, we aimed to identify X-chromosome-encoded proteins as a source of sex differences in IFN-I responses by pDCs. We identified the host-cell factor DDX3 as a key mediator for the sex dimorphism in the IFNα response. DDX3 was significantly higher expressed in female pDCs and was translocated together with IRF7 to the nucleus to orchestrate IFN-I transcription. DDX3 as driver of sex differences in the initial and chronic IFN-I response might serve as a novel target to limit IFN-I-mediated hyperactivation of immune cells. |
| format | Article |
| id | doaj-art-ac64126b4a384aeb98dab0429761ea16 |
| institution | DOAJ |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-ac64126b4a384aeb98dab0429761ea162025-08-20T03:07:17ZengElsevierPharmacological Research1096-11862025-06-0121610776410.1016/j.phrs.2025.107764The host cell factor DDX3 mediates sex dimorphism in the IFNα response of plasmacytoid dendritic cells upon TLR activationSebastian Schloer0Jana Hennesen1Lena Rueschpler2Mohamed Zamzamy3Felix Flomm4Wing Hang Ip5Andrea Pirosu6Thomas Dobner7Marcus Altfeld8Institute of Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg 20251, Germany; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg 20251, Germany; Corresponding authors at: Institute of Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg 20251, Germany.Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg 20251, GermanyInstitute of Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg 20251, Germany; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg 20251, GermanyInstitute of Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg 20251, Germany; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg 20251, GermanyResearch Department Virus Immunology, Leibniz Institute of Virology, Hamburg 20251, GermanyResearch Department Viral Transformation, Leibniz Institute of Virology, Hamburg 20251, GermanyResearch Department Virus Immunology, Leibniz Institute of Virology, Hamburg 20251, GermanyResearch Department Viral Transformation, Leibniz Institute of Virology, Hamburg 20251, GermanyInstitute of Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg 20251, Germany; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg 20251, Germany; Corresponding authors at: Institute of Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg 20251, Germany.During the course of viral infections, IFN-I producing pDCs are fundamental in establishing antiviral defense. However, little is known about the molecular mechanisms by which biological sex contributes to differences in IFN-I production by pDCs. Here, we aimed to identify X-chromosome-encoded proteins as a source of sex differences in IFN-I responses by pDCs. We identified the host-cell factor DDX3 as a key mediator for the sex dimorphism in the IFNα response. DDX3 was significantly higher expressed in female pDCs and was translocated together with IRF7 to the nucleus to orchestrate IFN-I transcription. DDX3 as driver of sex differences in the initial and chronic IFN-I response might serve as a novel target to limit IFN-I-mediated hyperactivation of immune cells.http://www.sciencedirect.com/science/article/pii/S1043661825001896Innate immunityPlasmacytoid dendritic cellsInterferonsSex differencesDDX3 |
| spellingShingle | Sebastian Schloer Jana Hennesen Lena Rueschpler Mohamed Zamzamy Felix Flomm Wing Hang Ip Andrea Pirosu Thomas Dobner Marcus Altfeld The host cell factor DDX3 mediates sex dimorphism in the IFNα response of plasmacytoid dendritic cells upon TLR activation Pharmacological Research Innate immunity Plasmacytoid dendritic cells Interferons Sex differences DDX3 |
| title | The host cell factor DDX3 mediates sex dimorphism in the IFNα response of plasmacytoid dendritic cells upon TLR activation |
| title_full | The host cell factor DDX3 mediates sex dimorphism in the IFNα response of plasmacytoid dendritic cells upon TLR activation |
| title_fullStr | The host cell factor DDX3 mediates sex dimorphism in the IFNα response of plasmacytoid dendritic cells upon TLR activation |
| title_full_unstemmed | The host cell factor DDX3 mediates sex dimorphism in the IFNα response of plasmacytoid dendritic cells upon TLR activation |
| title_short | The host cell factor DDX3 mediates sex dimorphism in the IFNα response of plasmacytoid dendritic cells upon TLR activation |
| title_sort | host cell factor ddx3 mediates sex dimorphism in the ifnα response of plasmacytoid dendritic cells upon tlr activation |
| topic | Innate immunity Plasmacytoid dendritic cells Interferons Sex differences DDX3 |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825001896 |
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