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Grünhagel, Benjamin; Borggrewe, Malte; Hagen, Sven Hendrik; Ziegler, Susanne M.; Henseling, Florian; Glau, Laura; Thiele, Rebecca-Jo; Pujantell, Maria; Sivayoganathan, Varshi; Padoan, Benedetta; Claussen, Janna M.; Düsedau, Arne; Hennesen, Jana; Bunders, Madeleine J.; Bonn, Stefan; Tolosa, Eva; Krebs, Christian F.; Dorn, Christoph; Altfeld, Marcus
iScience, 11/2023, Letnik: 26, Številka: 11Journal Article
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 to male pDCs, and both sex hormones and 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 of testosterone injections on TLR7-mediated IFN-I production by pDCs was assessed. Single-cell RNA analyses of pDCs showed downregulation of IFN-I-related gene expression signatures but also revealed transcriptional inter-donor heterogeneity. Longitudinal quantification showed continuous reduction of IFN-I protein production by pDCs and reduced expression of IFN-I-stimulated genes in peripheral blood mononuclear cells (PBMCs). These studies in trans men demonstrate that testosterone administration reduces IFN-I production by pDCs over time and provide insights into the immune-modulatory role of testosterone in sex-specific IFN-I-mediated immune responses. Display omitted •Longitudinal study of IFN-I pDC responses in 10 trans men•IFN-I production by pDCs upon TLR7/8 ligation decreased on mRNA and protein level•Downstream induction of interferon-stimulated genes was reduced•Data demonstrate regulation of the TLR7/8 pathway by sex hormones Health sciences; Patient social context; Gender
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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