Reduction of IFN-I responses by plasmacytoid dendritic cells in a longitudinal trans men cohort

• DOI: 10.1016/j.isci.2023.108209
• Publication Date: 2023-10-13T15:56:33Z
• Authors: Benjamin Grünhagel; Malte Borggrewe; Sven Hendrik Hagen; Susanne M. Ziegler; Florian Henseling; Laura Glau; Rebecca-Jo Thiele; Maria Pujantell; Varshi Sivayogana...; Benedetta Padoan; Janna M. Claussen; Arne Düsedau; Jana Hennesen; Madeleine J. Bunders; Stefan Bonn; Eva Tolosa; Christian F. Krebs; Christoph Dorn; Marcus Altfeld
• Keywords: TLR7; Plasmacytoid dendritic cell

Type I interferons (IFN-I) are important mediators of antiviral immunity and autoimmune diseases. Female plasmacytoid dendritic cells (pDCs) exert an elevated capacity to produce IFN-I upon toll-like receptor 7 (TLR7) activation compared male pDCs, both sex hormones X-encoded genes have been implicated in these sex-specific differences. Using longitudinal samples from a trans men cohort receiving gender-affirming hormone therapy (GAHT), the impact testosterone injections on TLR7-mediated production by pDCs was assessed. Single-cell RNA analyses showed downregulation IFN-I-related gene expression signatures but also revealed transcriptional inter-donor heterogeneity. Longitudinal quantification continuous reduction protein reduced IFN-I-stimulated peripheral blood mononuclear (PBMCs). These studies demonstrate that administration reduces over time provide insights into immune-modulatory role IFN-I-mediated immune responses.