Immunological control of skin development: from homeostasis to developmental pathologies

The skin serves not only as a physical barrier but also as a dynamic immune organ, where immune cells orchestrate tissue morphogenesis, homeostasis, and repair. Recent advances have revealed that immune cells play pivotal roles during skin development, guiding processes such as vascular formation, epidermal stratification, and hair follicle morphogenesis. In this review, we integrate fundamental mechanistic studies based on mouse models with key clinical observations from human diseases to comprehensively elucidate the contributions of critical immune cell populations-including macrophages, Langerhans cells, dendritic cells, mast cells, and innate lymphoid cells-to normal skin development. We then explore how dysregulation of immune cell functions leads to aberrant skin morphogenesis, contributing to congenital disorders, autoimmune-mediated abnormalities, and fibrotic diseases. By integrating insights from developmental immunology and pathology, we highlight how deviations in immune regulation can disrupt skin architecture and function. Understanding these mechanisms provides a foundation for developing targeted strategies to modulate immune pathways for therapeutic skin regeneration. Future studies integrating spatial and single-cell technologies will further refine our knowledge of immune-tissue crosstalk in skin development and disease.