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 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.
Authors
- Jana Hennesen
- Felix J. Flomm (ORCID: https://orcid.org/0000-0001-7691-0519)
- Wing-Hang Ip (ORCID: https://orcid.org/0000-0002-5367-1401)
- Marcus Altfeld (ORCID: https://orcid.org/0000-0001-5972-2997)
- Andrea Pirosu
- Sebastian Schloer (ORCID: https://orcid.org/0000-0002-9944-3017)
- Thomas Dobner (ORCID: https://orcid.org/0000-0001-7392-8588)
- Lena Rueschpler
- Mohamed Zamzamy
Institutions
- Leibniz Institute of Virology (LIV) (DE)
- Universität Hamburg (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Institute of Virology of the Slovak Academy of Sciences (SK)
Publication Details
- Journal
- Pharmacological Research
- Published
- 2025-05-10
- DOI
- https://doi.org/10.1016/j.phrs.2025.107764
- Citations
- 6
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 4.78
Funders
- Deutsche Forschungsgemeinschaft