Sex differences in the immune system are associated with higher susceptibility to numerous infectious diseases and cancers in males and, on the other hand, higher rates of autoimmune disorders in females. This fundamental phenomenon is further highlighted in the context of sex biases in melanoma outcomes, that both in incidence and survival rate, the male population across all ages having greater susceptibility than females. However, the mechanisms underlying sex-related differences in the immune system remain poorly understood. Dr. Chi’s preliminary data reveal that androgen signaling in males negatively regulates skin CD103+ dendritic cells (DCs) and type 2 innate lymphoid cells (ILC2s), which further impact the immune responses to microbial or inflammatory stimuli, both of which are key components in anti-tumor immune responses. In this proposal, Dr. Chi aims to investigate the underlying mechanism of androgen receptor (AR) signaling-driven sexual differences of skin immunity and its role in sexual dimorphism of skin diseases. He will first explore how AR signaling controls the level of DCs and ILC2s. Next, he will examine whether the AR-ILC2-DC axis determines sex differences of skin immunity upon bacterial colonization/infection and in melanoma. He will identify the key immune cells and cytokine signals in shaping sex disparity of skin immunity in the context of infection and melanoma.
This study should provide a comprehensive and mechanistic understanding of sex differences in anti-tumor responses in melanoma, which will promote the development of more efficient strategies for treating associated skin diseases.
Projects and Grants
Androgen receptor signaling negatively regulates the level of skin resident ILC2s and DCs, thereby shaping sex-specific skin immunity to commensals, pathogens, and melanoma
National Institute of Allergy and Infectious Diseases, NIH | Melanoma | 2022 | Yasmine Belkaid, Ph.D.
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