Skin immune sentinels play a critical role in maintaining skin health and responding to infections and diseases. Keratinocytes, the main cells of the epidermis, act as immune sentinels by sensing pathogens and triggering immune responses. They express Toll-like receptors (TLRs) that recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), leading to the activation of inflammatory pathways. Keratinocytes also produce antimicrobial peptides (AMPs) and cytokines that help defend against pathogens and regulate immune responses. In addition, keratinocytes can process and present antigens to T cells, contributing to immune surveillance. Dendritic cells (DCs), including CD103⁺ DCs, are strategically positioned to present antigens and initiate immune responses. Langerhans cells, a subset of DCs, are found in the epidermis and play a role in immune surveillance. However, recent studies suggest that tissue-resident DCs in the dermis are more important for immune responses in the skin. These DCs can cross-present antigens and activate T cells, contributing to immune homeostasis and pathology. T cells, particularly CD8⁺ T cells, are present in the skin and play a role in immune responses. Skin-resident T cells, including memory T cells, are strategically positioned to respond to antigen challenges and maintain immune homeostasis. These cells can be activated by DCs and contribute to immune responses in the skin. Unconventional T cells, such as γδ T cells and NKT cells, also play a role in skin immunity. γδ T cells can recognize stressed epithelial cells and contribute to immune surveillance, while NKT cells can recognize bacterial glycolipids and serve as antimicrobial immune sentinels. These cells help regulate immune responses and maintain skin homeostasis. Psoriasis is a chronic inflammatory skin disease characterized by the overactivation of immune cells, including T cells and DCs. The pathogenesis of psoriasis involves a complex interplay between genetic and environmental factors, leading to the dysregulation of immune responses. Key immune sentinels, including keratinocytes, DCs, and T cells, contribute to the development and progression of psoriasis. Understanding the role of skin immune sentinels is essential for developing new therapies for skin diseases. Research into these cells and their functions has provided important insights into the mechanisms of skin immunity and disease. Future studies will focus on translating these findings into clinical applications and developing targeted therapies for skin disorders.Skin immune sentinels play a critical role in maintaining skin health and responding to infections and diseases. Keratinocytes, the main cells of the epidermis, act as immune sentinels by sensing pathogens and triggering immune responses. They express Toll-like receptors (TLRs) that recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), leading to the activation of inflammatory pathways. Keratinocytes also produce antimicrobial peptides (AMPs) and cytokines that help defend against pathogens and regulate immune responses. In addition, keratinocytes can process and present antigens to T cells, contributing to immune surveillance. Dendritic cells (DCs), including CD103⁺ DCs, are strategically positioned to present antigens and initiate immune responses. Langerhans cells, a subset of DCs, are found in the epidermis and play a role in immune surveillance. However, recent studies suggest that tissue-resident DCs in the dermis are more important for immune responses in the skin. These DCs can cross-present antigens and activate T cells, contributing to immune homeostasis and pathology. T cells, particularly CD8⁺ T cells, are present in the skin and play a role in immune responses. Skin-resident T cells, including memory T cells, are strategically positioned to respond to antigen challenges and maintain immune homeostasis. These cells can be activated by DCs and contribute to immune responses in the skin. Unconventional T cells, such as γδ T cells and NKT cells, also play a role in skin immunity. γδ T cells can recognize stressed epithelial cells and contribute to immune surveillance, while NKT cells can recognize bacterial glycolipids and serve as antimicrobial immune sentinels. These cells help regulate immune responses and maintain skin homeostasis. Psoriasis is a chronic inflammatory skin disease characterized by the overactivation of immune cells, including T cells and DCs. The pathogenesis of psoriasis involves a complex interplay between genetic and environmental factors, leading to the dysregulation of immune responses. Key immune sentinels, including keratinocytes, DCs, and T cells, contribute to the development and progression of psoriasis. Understanding the role of skin immune sentinels is essential for developing new therapies for skin diseases. Research into these cells and their functions has provided important insights into the mechanisms of skin immunity and disease. Future studies will focus on translating these findings into clinical applications and developing targeted therapies for skin disorders.