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

- BM CD11b+ F4/80+ DCs were induced by rmGM-CSF and rmIL-4 successfully in vitro.
- BM CD11b+F4/80+ DC have therapeutic effect on mice CIA.
- The therapeutic role of BM CD11b+F4/80+ DC maybe depends on the induction of Foxp3+ Treg cells and BM CD11b+F4/80+ iDC' ability to suppress Th17 functions.
- BM CD11b+ F4/80+ DCs would provide a promising approach for the treatment of autoimmune diseases.

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.