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Publications

Journal Article Epublish 3 citations

PubMed: 40887533 DOI: 10.1038/s41598-025-15941-6

Sex hormones regulate the sexual dimorphism of the lung resident immune milieu.

Sci Rep 15(1):32032

Authors: Ioannis Belios, Tao Zhang, Christopher Urbschat, Jun Oh, Wolfgang Jungraithmayr, Samuel Huber, Petra C Arck, Anastasios D Giannou, Dimitra E Zazara

Affiliations

  • Division for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
  • Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, UKE, Hamburg, Germany.
  • University Children's Hospital, UKE, Hamburg, Germany.
  • Division of Thoracic Surgery, Rostock University Medical Center, Rostock, Germany.
  • Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
  • Department of Thoracic Surgery, Faculty of Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Hamburg Center for Translational Immunology, UKE, Hamburg, Germany.
  • Department of General, Visceral and Thoracic Surgery, UKE, Hamburg, Germany.
  • Division for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
  • University Children's Hospital, UKE, Hamburg, Germany.
  • Hamburg Center for Translational Immunology, UKE, Hamburg, Germany.
  • Division for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine and University Children's Hospital, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

Abstract

A strong sex-bias characterizes many respiratory immune diseases and has been attributed to sexually dimorphic immune responses. However, the role of lung-resident immunity in this context remains elusive. Here, we thoroughly characterized the lung-resident immune landscape in male and female mice, with a special focus on sex hormone effects in this context. Androgens were found to exert the strongest effects, markedly impacting B cells and neutrophils in both male and female lungs. Castrated males exhibited increased, while testosterone-treated females and males decreased lung-residing B cells. Testosterone supplementation of castrated males and females resulted in increased lung-residing neutrophils. Sex-mismatched orthotopic lung transplantation further supported these findings, since lungs isolated from female donors exhibited reduced tissue-residing B cells after their transplantation into male recipients. For the remaining lung-resident immune cell populations, sex differences were observed at the level of cell frequencies, with male lungs exhibiting higher frequencies of alveolar macrophages and lower frequencies of lung-resident dendritic cells and CD4⁺ tissue-resident memory T cells. Castration reversed some of these findings. Our findings highlight that the sexual dimorphism of the lung-resident immune landscape is modulated by sex hormones and especially androgens, thereby providing insights into the sex-specific manifestation of respiratory immune diseases.

MeSH

Cells, Lung, Neutrophils, Hormones, Immune System Diseases, Sex Characteristics, Immunity, Sex, Natural Science Disciplines, Tissues, Gonadal Steroid Hormones, Transplantation, Sex Differences