Monocyte-Derived Dendritic Cells Drive Skin Inflammation: Cellular Energy Metabolism and Microenvironmental Regulation

Background: Dendritic cells (DCs) represent a heterogeneous subpopulation of antigen-presenting cells that bridge the innate and acquired immune responses. Studies have reported that cellular metabolic reprogramming regulates the biological function of DCs, with distinct metabolic profiles characterizing different DC subsets and activation states. Particularly, blood monocyte-derived dendritic cells (mo-DCs) drive the skin inflammation. The differentiation, maturation, metabolism, and function of mo-DCs are influenced by microenvironmental factors, including pH, mechanical force, and temperature. Summary: The paper briefly reviewed the biological role of mo-DCs in skin diseases, focusing on their differentiation and phenotype, disease-associated metabolic adaptations, and the microenvironmental factors that influence their maturation, energy metabolism, and function. Future researchers should explore the impact of the skin microenvironment on the metabolism and function of mo-DCs and identify specific targets, which may pave the way for precision medicine methods for treating refractory inflammatory skin diseases. Key Messages: With the understanding of mo-DC metabolism and its regulation by microenvironmental factors, we have gained further insight into the mechanism of skin diseases. However, we still need to discover the role of the skin microenvironment in mo-DC metabolism and function.