Immune modulation by sex hormones: unveiling the complex interplay and regulatory networks

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.