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

AbstractBackgroundThe 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).MethodsThe expression of Foxp3 by DCs was evaluated by real‐time RT‐PCR, Western blotting, flow cytometry, and chromatin immunoprecipitation assay.ResultsWe observed that mice treated with SEB at 0.25–0.5 μg/mouse showed high frequencies of transforming growth factor (TGF)‐β‐producing CD4+ T cells and TGF‐β‐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 μg/mouse. Treating DCs with SEB in the culture induced high levels of Foxp3 at the TGF‐β 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.ConclusionDendritic cells have the capacity to express Foxp3, which can be upregulated by exposure to SEB.