Figure 2
From: Role of dendritic cells in the induction of regulatory T cells
DCs drive differentiation of foxp3+ inducible regulatory T cells. (iTregs). DCs secrete TGF-β, which induces foxp3 in naive T cells, driving differentiation of naive T cells into iTregs. Activation of AhR and TLR9 drives induction of IDO, which catalyzes tryptophan metabolism. Tryptophan metabolites promote iTreg generation through induction of TGF-β production and suppression of Th17 inducing cytokine, IL-6. Furthermore, uptake of apoptotic DCs by viable DCs along with exposure to haptens, glucocorticoids and UV radiation also induces TGF-β production, which drives iTreg differentiation. Other signals such as RANK/RANKL signalling by vitamin D treated keratinocytes and treatment of DCs with vasoactive intestinal peptide (VIP), hepatocyte growth factor (HGF) and prostaglandin-D2 (PGD2) also promote iTreg differentiation. Moreover, retinoic acid promotes iTreg differentiation by suppressing cytokines which are inhibitory to iTreg differentiation and targeting of antigen to DEC205 drives iTreg differentiation through a TGF-β dependent mechanism.