Protocol of generation of tolerogenic dendritic cells affects their transcriptional and metabolic profiles leading to specific tolerogenic functions.

Cell therapy is a promising approach for inducing tolerance and thus reducing the use of immunosuppressive drugs in several immune-mediated conditions. Tolerogenic dendritic cells (tolDCs) regulate antigen-specific tolerance and control the immune response, making them an interesting candidate for cell therapy. Over the last years, different human tolDCs have been generated ex vivo, each with specific phenotypic and functional characteristics. This study aims to highlight the impact of the manufacturing process on tolDC function. For that, two well-known tolDCs, autologous tolerogenic dendritic cells (ATDCs) and interleukin (IL)-10-induced dendritic cells (DC-10s), were compared based on their phenotype, metabolic secretion, transcriptomic profile, and their modulatory function. Our findings indicate that both ATDCs and DC-10s effectively regulate T cell responses; however, while DC-10s accomplish this through immune regulation, ATDCs rely on metabolic adaptations. Understanding these specific regulatory mechanisms is critically important in order to select the best disease to target using these tolDCs as cell-based therapy.