Friend or foe? — Janus Langerhans cells in skin immunity and promising clinical application

Langerhans cells (LCs), the professional antigen-presenting cells in the epidermis, serve as the first line of defense in the skin's immune system. With advancements in detection technologies and the development of diverse animal models, LCs have been shown to exhibit heterogeneous origins, phenotypes, and functions, which are regulated in a context-dependent manner by various cytokines and transcription factors. This heterogeneity enables LCs to either promote or suppress immune responses depending on the microenvironment. As research advances in elucidating the regulatory mechanisms underlying LC phenotypes and functions across various pathological conditions, clinical studies targeting LCs are gradually progressing. This review summarizes commonly used experimental animal models in LC research, highlights the phenotypic diversity of LCs in various diseases, and discusses their dual roles in disease progression. With our understanding of LC heterogeneity deepening, we anticipate elucidating the characteristic of distinct LC subgroups, thereby establishing a solid foundation for LC-targeted precision immunotherapy.