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TGF- β -induced regulatory T cells (iTregs) retain Foxp3 expression and immune-suppressive activity in collagen-induced arthritis (CIA). However, the mechanisms whereby transferred iTregs suppress immune responses, particularly the interplay between iTregs and dendritic cells (DCs)  in vivo , remain incompletely understood. In this study, we found that after treatment with iTregs, splenic CD11c + DCs, termed “DC iTreg ,” expressed tolerogenic phenotypes, secreted high levels of IL-10, TGF- β , and IDO, and showed potent immunosuppressive activity  in vitro . After reinfusion with DC iTreg , marked antiarthritic activity improved clinical scores and histological end-points were observed. The serological levels of inflammatory cytokines and anti-CII antibodies were low and TGF- β  production was high in the DC iTreg -treated group. DC iTreg  also induced new iTregs  in vivo . Moreover, the inhibitory activity of DC iTreg  on CIA was lost following pretreatment with the inhibitor of indoleamine 2,3-dioxygenase (IDO). Collectively, these findings suggest that transferred iTregs could induce tolerogenic characteristics in splenic DCs and these cells could effectively dampen CIA in an IDO-dependent manner. Thus, the potential therapeutic effects of iTregs in CIA are likely maintained through the generation of tolerogenic DCs  in vivo .

Tolerogenic Splenic IDO+Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis

Tolerogenic Splenic IDO⁺Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis