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Sökning: (WFRF:(Mikes P.)) > (2020-2023) > Immune system adapt...

Immune system adaptation during gender-affirming testosterone treatment

Consiglio, Camila (författare)
Lund University, Department of Laboratory Medicine, Lund, Sweden; Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Tadepally, Lakshmikanth (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Sardh, Fabian (författare)
Karolinska Institutet, Department of Medicine Solna, Solna, Sweden; Uppsala University, Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden
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Forlin, Rikard (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Wang, Jun (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Tan, Ziyang (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Barcenilla, Hugo (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Rodriguez, Lucie (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Sugrue, Jamie (författare)
Institut Pasteur, Université Paris Cité, Translational Immunology Unit, Paris, France
Noori, Peri (författare)
Karolinska Institutet, Department of Medicine Solna, Solna, Sweden
Páez, Laura P. (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Gonzalez, Laura (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Mugabo, Constantin H. (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Johnsson, Annette (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Hallgren, Åsa (författare)
Karolinska Institutet, Department of Medicine Solna, Solna, Sweden
Pou, Christian (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Chen, Yang (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Mikes, Jaromir (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
James, Anna (författare)
Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden
Dahlqvist, Per (författare)
Umeå University, Department of Public Health and Clinical Medicine, Umeå, Sweden
Wahlberg, Jeanette, 1969- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper
Hagelin, Anders (författare)
Karolinska University Hospital, ANOVA, Stockholm, Sweden; Karolinska Institutet, Department of Medicine Huddinge, Stockholm, Sweden
Holmberg, Mats (författare)
Karolinska University Hospital, ANOVA, Stockholm, Sweden; Karolinska Institutet, Department of Medicine Huddinge, Stockholm, Sweden
Degerblad, Marie (författare)
Karolinska Institutet, Endocrinology and Diabetes Unit, Department of Molecular Medicine and Surgery, Solna, Sweden
Isaksson, Magnus (författare)
Uppsala University, Department of Medical Sciences, Uppsala, Sweden
Duffy, Darragh (författare)
Institut Pasteur, Université Paris Cité, Translational Immunology Unit, Paris, France
Kämpe, Olle (författare)
Karolinska Institutet, Department of Medicine Solna, Solna, Sweden; Karolinska University Hospital, Center of Molecular Medicine, and Department of Endocrinology, Metabolism and Diabetes, Stockholm, Sweden
Landegren, Nils (författare)
Karolinska Institutet, Department of Medicine Solna, Solna, Sweden; Uppsala University, Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden
Brodin, Petter (författare)
Karolinska 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
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Lund University, Department of Laboratory Medicine, Lund, Sweden; Karolinska Institutet, Unit for Clinical Pediatrics, Dept of Women’s and Children’s Health, Solna, Sweden Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden (creator_code:org_t)
Elsevier, 2023
2023
Engelska.
Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 159, s. 29-30
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

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