title: Oral CD103-CD11b+classical dendritic cells present sublingual antigen and induce Foxp3+regulatory T cells in draining lymph nodes.
abstract: 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-β- 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.
authors.affiliation: Division of Oral Immunology, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai, Japan.|Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nagashima
authors.affiliation: Division of Oral Immunology, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai, Japan.|Division of Orthodontics and Dentofacial Orthopedics, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Bando
authors.affiliation: Division of Oral Immunology, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai, Japan.|Division of Oral Diagnosis, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.affiliation: Division of Oral Immunology, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ozaki
authors.affiliation: Division of Oral Immunology, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Morita
authors.affiliation: Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fukumoto
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Division of Oral Immunology, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sugawara
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D039001:Integrin alpha Chains / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D063729:Sublingual Immunotherapy / Q000379:methods*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000941:Antigens; D015703:Antigens, CD; D039481:CD11b Antigen; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D039001:Integrin alpha Chains; C091367:alpha E integrins; D010047:Ovalbumin