DCs drive differentiation of Tr1 regulatory T cells. DCs secrete IL-27, IL-10 and TGF-β1, which induce AhR and c-maf in T cells. AhR and c-maf physically associate with each other and activate IL-10 and IL-21 promoters, driving Tr1 differentiation. IL-27 suppresses production of Th17 inducing cytokines such as IL-1β, IL-6 and IL-23 and drives Tr1 differentiation. IFN-γ suppresses Th17 inducing osteoprotegerin (OPG) and drives IL-27 production, thereby promoting Tr1 differentiation. Furthermore, PD-1/PDL-1 signaling and bacterial peptides along with vasoactive intestinal peptide (VIP) drive IL-10 production which also induces Tr1 differentiation. Moreover, ICOS/ICOSL signalling as well as TGF-β production by DCs has also been implicated in driving Tr1 differentiation.