Bone marrow CD11b⁺F4/80⁺ dendritic cells ameliorate collagen-induced arthritis through modulating the balance between Treg and Th17

Tolerogenic dendritic cells (DCs) are well-known to show an immunosuppressive function. In this study we determine the therapeutic effects and potential mechanisms of transferred bone marrow (BM) CD11b⁺F4/80⁺ DCs on collagen-induced arthritis (CIA) in mice. Murine BM CD11b⁺F4/80⁺ DCs were generated under the stimulation of GM-CSF and IL-4, and the function of BM CD11b⁺ F4/80⁺ DCs was identified by measuring the levels of IL-10, TGF-beta and indoleamine 2,3-dioxygenase (IDO). BM CD11b⁺F4/80⁺ DCs were transferred to CIA mice by intravenous injections. The histopathology of joint and spleen were evaluated. T lymphocyte proliferation, Treg and Th17 subsets were analyzed. The expressions of Foxp3, Helios and RORγt in T lymphocytes co-cultured with BM CD11b⁺F4/80⁺ DCs were measured in vitro. We found that BM CD11b⁺F4/80⁺ DCs induced by GM-CSF and IL-4 could express high levels of IL-10, TGF-beta and IDO. BM CD11b⁺F4/80⁺ DCs significantly reduced the pathologic scores in joints and spleens, which correlated significantly with the reduced T lymphocyte proliferation and Th17 cell number, and with the increased Tregs number. In vitro, OVA-pulsed BM CD11b⁺F4/80⁺ DCs promoted Treg cell expansion, enhanced IL-10 and CTLA-4 protein expression, augmented Foxp3 and Helios mRNA expression, and inhibited RORγt and IL-17 mRNA expression. Taken together, BM CD11b⁺F4/80⁺ DCs are able to ameliorate the development and severity of CIA, at least partly by inducing Foxp3⁺ Treg cell expansion and suppressing Th17 function. The BM CD11b⁺F4/80⁺ DCs might have a promising immunotherapeutic potential for autoimmune arthritis.