FICZ generates human tDCs that induce CD4⁺ CD25^high Foxp3⁺ Treg-like cell differentiation

Dendritic cells (DCs) play a central role in the maintenance of immune homeostasis, their participation as professional antigen presenting cells is essential to the initiation of the adaptive immune response as well as to the induction of tolerance. The recently described role of the aryl hydrocarbon receptor (AhR) in the immune system, particularly in the modulation of the adaptive immune response has attracted the attention as a potential player in the induction of immune tolerance. However, the effects of AhR activation through endogenous ligands on human DCs have been poorly evaluated. In this study, we investigated the effect of FICZ, a natural AhR ligand, on monocyte-derived dendritic cells (Mo-DCs) from healthy subjects. We found that the activation of AhR through FICZ during DCs differentiation and maturation processes resulted in a decreased expression of CD83, an increased expression of the enzyme IDO and a reduced production of the pro-inflammatory cytokines IL-6 and TNF-α. More importantly, FICZ-treated DCs were able to induce the differentiation of naive T lymphocytes into CD4⁺ CD25^high Foxp3⁺ T reg-like cells. Our results show that the activation of the AhR on human DCs induces a tolerogenic phenotype with potential implications in immunotherapy.