Forkhead box protein-3 (Foxp3)-producing dendritic cells suppress allergic response.

Background: The generation of the tolerogenic dendritic cells (DC) is not fully understood yet. Forkhead box protein-3 (Foxp3) is an important molecule in the immune tolerance. This study tests a hypothesis that DCs express Foxp3, which can be upregulated by Staphylococcal enterotoxin B (SEB). Methods: The expression of Foxp3 by DCs was evaluated by real-time RT-PCR, Western blotting, flow cytometry, and chromatin immunoprecipitation assay. Results: We observed that mice treated with SEB at 0.25-0.5 mu g/mouse showed high frequencies of transforming growth factor (TGF)-beta-producing CD4(+) T cells and TGF-beta-producing DCs in the intestine, while the IL-4(+) CD4(+) T cells and TIM4(+) DCs were dominated in the intestine in mice treated with SEB at 1-10 mu g/mouse. Treating DCs with SEB in the culture induced high levels of Foxp3 at the TGF-beta promoter locus. The function of Foxp3 was blocked by STAT6 (signal transducer and activator transcription-6); the latter was induced by exposing DCs to SEB in the culture at doses of 100-400 ng/ml. Treating allergic mice with specific immunotherapy (SIT) together with SEB significantly promoted the therapeutic effects on the allergic responses than treating with SIT alone. Conclusion: Dendritic cells have the capacity to express Foxp3, which can be upregulated by exposure to SEB.