Collectively, our findings suggest that the mechanism responsible for the protective effect of SLIT on deleterious allergic diseases involves the mucosal tolerance that requires the existence of cDCs rather than the shift in the TH1/TH2 balance, and ManLNs serve as primary sites to generate antigen-specific CD4+Foxp3+ pTreg cells for establishing mucosal tolerance, which is different process from the induction of oral tolerance that triggered in MesLNs upon exposure to dietary constituents in intestines. This evidence concerns the gene FOXP3 and allergic disease.