MINI REVIEW article

Front. Immunol.

Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1501959

This article is part of the Research TopicGender Affirming Hormone Therapy and its Immunological ImplicationsView all articles

Epigenetic remodelling by sex hormone receptors and implications for gender affirming hormone therapy

Provisionally accepted
Den CelestraDen Celestra1Nhi NL NguyenNhi NL Nguyen2Camille LaberthonniereCamille Laberthonniere3Ken PangKen Pang2Richard SafferyRichard Saffery1Rachel A DaveyRachel A Davey4Musa MhlangaMusa Mhlanga3Ada CheungAda Cheung4Boris NovakovicBoris Novakovic1*
  • 1Cell Biology, Development and Disease, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia
  • 2Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia
  • 3Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, Netherlands
  • 4Austin Health, University of Melbourne, Melbourne, Victoria, Australia

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Sex differences in immune system development and response to pathogens has been well documented, with females exhibiting more favourable outcomes for certain infections but a higher incidence of autoimmune disease compared to males. At least some of these sex differences are mediated by sex hormones, which signal through sex hormone receptors to remodel the regulatory chromatin landscape of cells. Here, we summarise the current knowledge of how sex hormone receptors remodel chromatin structure and epigenetic marks in different contexts in humans. As the epigenome is fundamental to specifying cell identity and function, and reflects past exposures, epigenetic variation can influence cellular responses to future stimuli. This has implications for susceptibility to infection and complex inflammatory disease in a range of hormone therapy settings, including gender-affirming hormone therapy in transgender people. Therefore, profiling of epigenetic marks in the context of gender-affirming hormone therapy is an important unexplored field of research.

Keywords: epigenetics, sex hormones, estrogen, Testosterone, estrogen receptor, Gender-affirming hormonal therapy, gender, Immunity

Received: 26 Sep 2024; Accepted: 17 Apr 2025.

Copyright: © 2025 Celestra, Nguyen, Laberthonniere, Pang, Saffery, Davey, Mhlanga, Cheung and Novakovic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Boris Novakovic, Cell Biology, Development and Disease, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, 3052, VIC, Australia

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material