Dendritic Cells from Oral Cavity Induce Foxp3+ Regulatory T Cells upon Antigen Stimulation

Evidence is accumulating that dendritic cells (DCs) from the intestines have the capacity to induce Foxp3(+)CD4(+) regulatory T cells (T-regs) and regulate immunity versus tolerance in the intestines. However, the contribution of DCs to controlling immunity versus tolerance in the oral cavity has not been addressed. Here, we report that DCs from the oral cavity induce Foxp3(+) T-regs as well as DCs from intestine. We found that oral-cavity-draining cervical lymph nodes contained higher frequencies of Foxp3(+) T-regs and ROR-γt(+) CD4(+)T cells than other lymph nodes. The high frequency of Foxp3(+) T-regs in the oral-cavity-draining cervical lymph nodes was not dependent on the Toll like receptor (TLR) adaptor molecules, Myd88 and TICAM-1 (TRIF). In contrast, the high frequency of ROR-γt(+) CD4(+)T cells relies on Myd88 and TICAM-1. In vitro data showed that CD11c(+) DCs from oral-cavity-draining cervical lymph nodes have the capacity to induce Foxp3(+) T-regs in the presence of antigen. These data suggest that, as well as in the intestinal environment, antigen-presenting DCs may play a vital role in maintaining tolerance by inducing Foxp3(+) T-regs in the oral cavity.