Abstract
Cutaneous antigen-presenting cells (APCs), particularly dendritic cells (DCs) and Langerhans cells (LCs), are a diverse population of cells that play a vital role in immune surveillance by initiating and shaping skin immune responses. They link innate and adaptive immunity by presenting antigens, migrating, and activating T lymphocytes, thereby acting as orchestrators of tissue immunity. This review provides an updated overview of the morphofunctional diversity of cutaneous APCs, ranging from epidermal LCs and DCs, to dermal conventional DCs (DC1/DC2), plasmacytoid DCs (pDCs), including newly defined subsets such as DC3, Axl(+)Siglec-6(+) DCs (ASDCs) and LAMP3(+) mature regulatory DCs (mRegDCs). Dynamic differences in APC composition and function between homeostatic and inflamed skin are discussed, with particular emphasis on inflammatory and autoimmune conditions such as psoriasis, lupus erythematosus and chronic atopic dermatitis, in which distinct DC subsets contribute to Th1 and Th17 immune circuits. This review is the first skin-related approach that extensively discusses the cutaneous role of APCs in the neuro-immune-cutaneous axis, as well as their interactions with the local microenvironment. Ongoing controversies regarding the classification and stability of certain DC populations are discussed. A better understanding of the diversity, migration mechanisms and microenvironmental interactions of cutaneous APCs could lead to the identification of new biomarkers and therapeutic targets for inflammatory, autoimmune, and oncological skin diseases.