Friday, July 17, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Sublingual immunotherapy is safe and efficient for the treatment of type I allergies, but the underlying immunological mechanisms, particularly induction of regulatory T (Treg) cells, are still unclear. Here we show that sublingual application of ovalbumin induced Foxp3+ Treg cells in the draining submandibular LNs (ManLNs) in mice. In the lingual and sublingual tissues, oral classical dendritic cells (cDCs) were clearly separated from oral macrophages by flow cytometry and expanded in vivo by DC differentiation cytokine Flt3 ligand. Oral cDCs showed retinoic acid (RA)-producing activity and converted naive CD4+ T cells to Foxp3+ Treg cells in a TGF-β and RA dependent manner in vitro. In the ManLNs, migratory cDCs also showed RA-producing activity. After sublingual application of fluorescent ovalbumin, fluorescence was detected in oral macrophages in the tissues followed by migratory cDCs in the ManLNs, and the sublingual ovalbumin-primed migratory cDCs induced Foxp3+ Treg cell conversion ex vivo, suggesting that oral macrophages incorporate sublingual antigens and presumably transfer them to oral cDCs in the sublingual mucosa, and that the antigen-incorporated cDCs migrate to the ManLNs and induce Treg cells. These results highlight the mechanism and pathway by which Foxp3+ Treg cells may be induced by sublingual immunotherapy.