REVIEW article
Front. Immunol.
Sec. Systems Immunology
This article is part of the Research TopicSex Differences in Immune Responses to Cardiovascular DiseaseView all articles
Immune Modulation by Sex Hormones: Unveiling the Complex Interplay and Regulatory Networks
Provisionally accepted
- 1First Affiliated Hospital of Harbin Medical University, Harbin, China
- 2Nanjing University Model Animal Research Center, Nanjing, China
- 3Nanjing University Medical School, Nanjing, China
- 4Ruijin-Hainan Hospital Shanghai Jiao Tong University School of Medicine, Qionghai, China
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Sex hormones, androgens, estrogens, and progestogens, play critical regulatory roles in the development and activation of the immune system, which contribute to the sex dimorphism in the disease susceptibility. Sex hormone receptors are expressed in various of immune cells as well as epithelial and stromal cells, implying both direct and indirect effects of sex hormones. Immune system homeostasis can be disrupted by fluctuations in sex hormone levels, which occur during physiological states such as pregnancy and aging, under the influence of the microbiota, or upon exposure to endocrine disruptors. All of these factors have potential impacts on the immune system homeostasis. Here, we provide an overview of the sex hormone system and how sex hormones affect the immune system. Additionally, we highlight the roles of epithelial and stromal cells in the sex hormone-immune crosstalk and discuss key factors that affect sex hormone levels and have potential regulatory effects on immune balance.
Keywords: Aging, Hormone disruptors, immune response, Pregnancy, sex differences, sex hormones
Received: 17 Nov 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Wan, Chen, Shan and Chi. 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: Liang Chi
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