title: Repeated antigen painting and sublingual immunotherapy in mice convert sublingual dendritic cell subsets.
abstract: The sublingual mucosa (SLM) is utilized as the site for sublingual immunotherapy (SLIT) to induce tolerance against allergens. The contribution of SLM-dendritic cells (SLM-DCs) has not been clarified. The aim of this study was to examine the dynamics and phenotype of SLM-DCs after topical antigen painting and SLIT. SLM-DCs were histologically evaluated after FITC painting. A novel murine Japanese cedar pollinosis (JCP) model was generated and change in SLM-DCs after SLIT was examined. The density of SLM-DCs was clearly lower compared with the buccal mucosa and dorsal surface of the tongue. Topical FITC painting on the SLM induced maximal recruitment of submucosal DCs (smDCs) at 6h, but most smDCs had vanished at 24h. Repeated painting on the SLM induced exhaustion and conversion of the smDC phenotype. CD206(high)CD11c(low) round-type cells with fewer dendrites and less lymph node migration capacity became dominant. In the murine model of JCP, SLIT efficiently inhibited clinical symptoms and allergen-mediated immunological responses. SLIT markedly reduced the number of SLM-DCs, converted to the round-type dominant phenotype and inhibited the activation of regional lymph node DCs. Topical antigen painting on the SLM induced rapid exhaustion and conversion of smDCs. The unique dynamics of SLM-DCs may contribute to tolerance induction in SLIT.
authors.affiliation: Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8547, Japan.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8547, Japan.
authors.forename: Tatsukuni
authors.initials: T
authors.lastname: Ohno
authors.affiliation: Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8547, Japan.
authors.forename: Siwen
authors.initials: S
authors.lastname: Kang
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Takai
authors.affiliation: Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8547, Japan. Electronic address: miyuki.mim@tmd.ac.jp.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Azuma
mesh_terms: D000286:Administration, Sublingual; D000485:Allergens / Q000276:immunology; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D037181:Lectins, C-Type / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa / Q000166:cytology / Q000276:immunology*; D011058:Pollen / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology; D063729:Sublingual Immunotherapy / Q000379:methods*
chemical_list: D000485:Allergens; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface
keywords: Dendritic cells; Oral mucosa; Pollinosis; Sublingual immunotherapy; Sublingual mucosa