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

Sex differences in immune system development and response to pathogens has been well documented, with females exhibiting more favorable 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,...

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Main Authors: Den Celestra, Nhi N. L. Nguyen, Camille Laberthonniere, Ken C. Pang, Richard Saffery, Rachel A. Davey, Musa Mhlanga, Ada S. Cheung, Boris Novakovic
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1501959/full
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author Den Celestra
Nhi N. L. Nguyen
Camille Laberthonniere
Ken C. Pang
Ken C. Pang
Richard Saffery
Rachel A. Davey
Musa Mhlanga
Ada S. Cheung
Ada S. Cheung
Boris Novakovic
author_facet Den Celestra
Nhi N. L. Nguyen
Camille Laberthonniere
Ken C. Pang
Ken C. Pang
Richard Saffery
Rachel A. Davey
Musa Mhlanga
Ada S. Cheung
Ada S. Cheung
Boris Novakovic
author_sort Den Celestra
collection DOAJ
description Sex differences in immune system development and response to pathogens has been well documented, with females exhibiting more favorable 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 summarize 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.
format Article
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institution Kabale University
issn 1664-3224
language English
publishDate 2025-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-7fc3e78ffb424f1eaa8aea2fca6441fd2025-08-20T03:52:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15019591501959Epigenetic remodeling by sex hormone receptors and implications for gender affirming hormone therapyDen Celestra0Nhi N. L. Nguyen1Camille Laberthonniere2Ken C. Pang3Ken C. Pang4Richard Saffery5Rachel A. Davey6Musa Mhlanga7Ada S. Cheung8Ada S. Cheung9Boris Novakovic10Murdoch Children’s Research Institute and Department of Pediatrics, The University of Melbourne, Parkville, VIC, AustraliaMurdoch Children’s Research Institute and Department of Pediatrics, The University of Melbourne, Parkville, VIC, AustraliaRadboud Institute for Molecular Life Sciences RIMLS, Radboud University Medical Center, Nijmegen, NetherlandsMurdoch Children’s Research Institute and Department of Pediatrics, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Adolescent Medicine, Royal Children’s Hospital, Parkville, VIC, AustraliaMurdoch Children’s Research Institute and Department of Pediatrics, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Medicine Austin Health, University of Melbourne, Heidelberg, VIC, AustraliaRadboud Institute for Molecular Life Sciences RIMLS, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Medicine Austin Health, University of Melbourne, Heidelberg, VIC, AustraliaDepartment of Endocrinology, Austin Health, Melbourne, VIC, AustraliaMurdoch Children’s Research Institute and Department of Pediatrics, The University of Melbourne, Parkville, VIC, AustraliaSex differences in immune system development and response to pathogens has been well documented, with females exhibiting more favorable 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 summarize 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1501959/fullepigeneticssex hormonesestrogentestosteroneestrogen receptorgender-affirming hormonal therapy
spellingShingle Den Celestra
Nhi N. L. Nguyen
Camille Laberthonniere
Ken C. Pang
Ken C. Pang
Richard Saffery
Rachel A. Davey
Musa Mhlanga
Ada S. Cheung
Ada S. Cheung
Boris Novakovic
Epigenetic remodeling by sex hormone receptors and implications for gender affirming hormone therapy
Frontiers in Immunology
epigenetics
sex hormones
estrogen
testosterone
estrogen receptor
gender-affirming hormonal therapy
title Epigenetic remodeling by sex hormone receptors and implications for gender affirming hormone therapy
title_full Epigenetic remodeling by sex hormone receptors and implications for gender affirming hormone therapy
title_fullStr Epigenetic remodeling by sex hormone receptors and implications for gender affirming hormone therapy
title_full_unstemmed Epigenetic remodeling by sex hormone receptors and implications for gender affirming hormone therapy
title_short Epigenetic remodeling by sex hormone receptors and implications for gender affirming hormone therapy
title_sort epigenetic remodeling by sex hormone receptors and implications for gender affirming hormone therapy
topic epigenetics
sex hormones
estrogen
testosterone
estrogen receptor
gender-affirming hormonal therapy
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1501959/full
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