Celestra Den, Nguyen Nhi N L, Laberthonniere Camille, Pang Ken C, Saffery Richard, Davey Rachel A, Mhlanga Musa, Cheung Ada S, Novakovic Boris
Murdoch Children's Research Institute and Department of Pediatrics, The University of Melbourne, Parkville, VIC, Australia.
Radboud Institute for Molecular Life Sciences RIMLS, Radboud University Medical Center, Nijmegen, Netherlands.
Front Immunol. 2025 May 8;16:1501959. doi: 10.3389/fimmu.2025.1501959. eCollection 2025.
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.
免疫系统发育及对病原体反应方面的性别差异已有充分记录，与男性相比，女性在某些感染中表现出更有利的结果，但自身免疫性疾病的发病率更高。这些性别差异中至少有一些是由性激素介导的，性激素通过性激素受体发出信号，重塑细胞的调节染色质格局。在此，我们总结了目前关于性激素受体如何在人类不同背景下重塑染色质结构和表观遗传标记的知识。由于表观基因组对于确定细胞身份和功能至关重要，并反映过去的暴露情况，表观遗传变异会影响细胞对未来刺激的反应。这对一系列激素治疗环境下的感染易感性和复杂炎症性疾病具有影响，包括跨性别者的性别确认激素治疗。因此，在性别确认激素治疗背景下对表观遗传标记进行分析是一个重要的未被探索的研究领域。
