The study investigates the mechanisms underlying sexual dimorphism in skin immunity, focusing on the role of type 2 innate lymphoid cells (ILC2) and the androgen-ILC2-dendritic cell (DC) axis. Key findings include: 1. **Sexual Dimorphism in Skin Immunity**: Males and females exhibit significant differences in immune responses and disease susceptibility, particularly in the skin. Females generally show stronger immune responses to infections and vaccines, and have a higher incidence of autoimmune disorders. 2. **Androgen Regulation of ILC2**: Androgens negatively regulate ILC2, leading to reduced DC accumulation and activation in males, resulting in lower tissue immunity. This regulation is mediated through the androgen receptor (AR). 3. **ILC2 as a Mediator**: ILC2 plays a crucial role in shaping sexual immune dimorphism. They are enriched in females and express higher levels of AR, which is responsible for their negative regulation by androgens. ILC2 produce granulocyte-macrophage colony-stimulating factor (GM-CSF), which is essential for the homeostasis and activation of DCs. 4. **DC Homeostasis**: The density and activation of DC subsets in the skin are significantly higher in females compared to males. This is partly due to the higher number of ILC2, which produce GM-CSF and restore cDC1 (a type of DC) in female-specific models. 5. **Microbiota's Role**: The microbiota further shapes immune bias in the skin, particularly by enhancing type 17 responses in females. This suggests that the microbiota can calibrate the tone of local immunity, which is controlled by sex hormones. 6. **Conclusion**: The study proposes that sexual dimorphism in skin immunity is primarily controlled by the strength of the resident DC network, with ILC2 acting as a key mediator. The interaction between sex hormones and the microbiota defines the set points of tissue immune responses, with hormones controlling the strength and the microbiota calibrating the tone. This work highlights the importance of understanding the interplay between sex hormones, ILC2, and the microbiota in shaping tissue-specific immune responses, providing insights into the mechanisms underlying sexual dimorphism in immunity.The study investigates the mechanisms underlying sexual dimorphism in skin immunity, focusing on the role of type 2 innate lymphoid cells (ILC2) and the androgen-ILC2-dendritic cell (DC) axis. Key findings include: 1. **Sexual Dimorphism in Skin Immunity**: Males and females exhibit significant differences in immune responses and disease susceptibility, particularly in the skin. Females generally show stronger immune responses to infections and vaccines, and have a higher incidence of autoimmune disorders. 2. **Androgen Regulation of ILC2**: Androgens negatively regulate ILC2, leading to reduced DC accumulation and activation in males, resulting in lower tissue immunity. This regulation is mediated through the androgen receptor (AR). 3. **ILC2 as a Mediator**: ILC2 plays a crucial role in shaping sexual immune dimorphism. They are enriched in females and express higher levels of AR, which is responsible for their negative regulation by androgens. ILC2 produce granulocyte-macrophage colony-stimulating factor (GM-CSF), which is essential for the homeostasis and activation of DCs. 4. **DC Homeostasis**: The density and activation of DC subsets in the skin are significantly higher in females compared to males. This is partly due to the higher number of ILC2, which produce GM-CSF and restore cDC1 (a type of DC) in female-specific models. 5. **Microbiota's Role**: The microbiota further shapes immune bias in the skin, particularly by enhancing type 17 responses in females. This suggests that the microbiota can calibrate the tone of local immunity, which is controlled by sex hormones. 6. **Conclusion**: The study proposes that sexual dimorphism in skin immunity is primarily controlled by the strength of the resident DC network, with ILC2 acting as a key mediator. The interaction between sex hormones and the microbiota defines the set points of tissue immune responses, with hormones controlling the strength and the microbiota calibrating the tone. This work highlights the importance of understanding the interplay between sex hormones, ILC2, and the microbiota in shaping tissue-specific immune responses, providing insights into the mechanisms underlying sexual dimorphism in immunity.