Leveraging current insights on IL-10-producing dendritic cells for developing effective immunotherapeutic approaches.

Dendritic cells (DC) are professional antigen-presenting cells involved in promoting and controlling immune responses. Different subsets of DC, named tolerogenic (tol)DC, play a critical role in the maintenance of tissue homeostasis and in fostering tolerance. These unique skills make tolDC especially attractive for strategies aimed at re-establishing/inducing tolerance in immune-mediated conditions. The generation of potent tolDC in vitro from peripheral blood monocytes has seen remarkable advancements. TolDC modulate T cell dynamics by favoring regulatory T cells (Tregs) and curbing effector/pathogenic T cells. Among the several methods developed for in vitro tolDC generation, IL-10 conditioning has been proven to be the most efficient, as IL-10-modulated tolDC were demonstrated to promote Tregs with the strongest suppressive activities. Investigating the molecular, metabolic, and functional profiles of tolDC uncovers essential pathways that facilitate their immunoregulatory functions. This Review provides an overview of current knowledge on the role of tolDC in health and disease, focusing on IL-10 production, functional characterization of in vitro generated tolDC, molecular and metabolic changes occurring in tolDC induced by tolerogenic agents, clinical applications of tolDC-based therapy, and finally new perspectives in the generation of effective tolDC.