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  • Consiglio, CamilaLund University, Department of Laboratory Medicine, Lund, Sweden; Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)

Immune system adaptation during gender-affirming testosterone treatment

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • Elsevier,2023
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:oru-109078
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-109078URI
  • https://doi.org/10.1016/j.jri.2023.104065DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:153798783URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:vet swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Biological sex impacts human immune responses, modulating susceptibility and severity to immune-related diseases. Female generally mount more robust immune responses than males, resulting in lower infection severity and greater autoimmunity incidence. Here, we addressed the contribution of testosterone to human immune function by analyzing a cohort of subjects undergoing gender-affirming testosterone treatment. We performed systems-level immunomonitoring through mass cytometry, scRNA and scA-TAC-Sequencing, and proteome profiling of blood samples at baseline and following 3 and 12 months of treatment. Testosterone treatment was associated with a low-grade inflammatory profile, evidenced by upregulation of proinflammatory plasma proteome (e.g., EN-RAGE, OSM, TNF), and induction of an inflammatory transcriptional program associated with NFkB signaling, and TNF signaling. Following testosterone treatment, higher NFkB activity was revealed in CD4 T, CD8 T, and NK cells in scATACseq analyses. Further, testosterone increased monocytic inflammatory responses upon bacterial stimulation in vitro. Although testosterone was associated with this inflammatory profile, it also exerted negative effects on antiviral immunity. Firstly, the percentage of plasmacytoid dendritic cells (pDC) decreased over transition, with pDC also displaying phenotypic changes associated with lower IFN responses. Secondly, bulk transcriptomics analyses show an overall reduction of IFNa responses. Thirdly, testosterone treatment led to reduced IFNa production upon PBMCs stimulation with a viral agonist. Our results show that testosterone has broad effects on the human immune system, and significantly modulates important players in antiviral immunity and inflammatory response. Identifying pathways involved in immune sexual dimorphism will help define novel targets for effective prevention and treatment of immune-mediated diseases.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Tadepally, LakshmikanthKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • Sardh, FabianKarolinska Institutet, Department of Medicine Solna, Solna, Sweden; Uppsala University, Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden (author)
  • Forlin, RikardKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • Wang, JunKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • Tan, ZiyangKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • Barcenilla, HugoKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • Rodriguez, LucieKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • Sugrue, JamieInstitut Pasteur, Université Paris Cité, Translational Immunology Unit, Paris, France (author)
  • Noori, PeriKarolinska Institutet, Department of Medicine Solna, Solna, Sweden (author)
  • Páez, Laura P.Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • Gonzalez, LauraKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • Mugabo, Constantin H.Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • Johnsson, AnnetteKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • Hallgren, ÅsaKarolinska Institutet, Department of Medicine Solna, Solna, Sweden (author)
  • Pou, ChristianKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • Chen, YangKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • Mikes, JaromirKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • James, AnnaKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (author)
  • Dahlqvist, PerUmeå University, Department of Public Health and Clinical Medicine, Umeå, Sweden (author)
  • Wahlberg, Jeanette,1969-Örebro universitet,Institutionen för medicinska vetenskaper(Swepub:oru)jewg (author)
  • Hagelin, AndersKarolinska University Hospital, ANOVA, Stockholm, Sweden; Karolinska Institutet, Department of Medicine Huddinge, Stockholm, Sweden (author)
  • Holmberg, MatsKarolinska University Hospital, ANOVA, Stockholm, Sweden; Karolinska Institutet, Department of Medicine Huddinge, Stockholm, Sweden (author)
  • Degerblad, MarieKarolinska Institutet, Endocrinology and Diabetes Unit, Department of Molecular Medicine and Surgery, Solna, Sweden (author)
  • Isaksson, MagnusUppsala University, Department of Medical Sciences, Uppsala, Sweden (author)
  • Duffy, DarraghInstitut Pasteur, Université Paris Cité, Translational Immunology Unit, Paris, France (author)
  • Kämpe, OlleKarolinska Institutet, Department of Medicine Solna, Solna, Sweden; Karolinska University Hospital, Center of Molecular Medicine, and Department of Endocrinology, Metabolism and Diabetes, Stockholm, Sweden (author)
  • Landegren, NilsKarolinska Institutet, Department of Medicine Solna, Solna, Sweden; Uppsala University, Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden (author)
  • Brodin, PetterKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden; Imperial College London, Department of Immunology and Inflammation, London, UK (author)
  • Lund University, Department of Laboratory Medicine, Lund, Sweden; Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, SwedenKarolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (creator_code:org_t)

Related titles

  • In:Journal of Reproductive Immunology: Elsevier159, s. 29-300165-03781872-7603

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