| First Author | Tanaka Y | Year | 2017 |
| Journal | Mucosal Immunol | Volume | 10 |
| Issue | 1 | Pages | 79-90 |
| PubMed ID | 27166558 | Mgi Jnum | J:347155 |
| Mgi Id | MGI:6147881 | Doi | 10.1038/mi.2016.46 |
| Citation | Tanaka Y, et al. (2017) Oral CD103(-)CD11b(+) classical dendritic cells present sublingual antigen and induce Foxp3(+) regulatory T cells in draining lymph nodes. Mucosal Immunol 10(1):79-90 |
| abstractText | Sublingual immunotherapy (SLIT) is a safe and efficient treatment for type 1 allergies; however, the underlying immunological mechanisms, particularly the phenotype of oral antigen-presenting cells (APCs) responsible for the induction of regulatory T (Treg) cells, remain unclear. We show here that the sublingual application of ovalbumin (OVA) induced antigen-specific Foxp3(+) Treg cells in draining submandibular lymph nodes (ManLNs). Oral APCs were classified into macrophages, classical dendritic cells (cDCs), and Langerhans cells by flow cytometry. A major subset of oral cDCs with the CD103(-)CD11b(+) phenotype showed retinoic acid (RA)-producing activity and converted naive CD4(+) T cells to Foxp3(+) Treg cells in a transforming growth factor-beta- and RA-dependent manner in vitro. In the ManLNs, migratory CD103(-)CD11b(+) cDCs also showed RA-producing activity. After the sublingual application of fluorescent OVA, fluorescence was detected in oral macrophages in tissues, followed by migratory CD103(-)CD11b(+) cDCs in ManLNs and migratory CD103(-)CD11b(+) cDCs were the main APCs responsible for the induction of sublingual antigen-specific Treg cells. The transfer of OVA-SLIT-induced Treg cells suppressed the OVA-induced hypersensitivity response. These results suggest that oral CD103(-)CD11b(+) cDCs transport sublingual antigens to draining ManLNs and induce antigen-specific Foxp3(+) Treg cells, and, thus, provide a rationale for developing cDC-based therapeutic approaches in SLIT. |
