title: Dendritic cells from oral cavity induce Foxp3(+) regulatory T cells upon antigen stimulation.
abstract: Evidence is accumulating that dendritic cells (DCs) from the intestines have the capacity to induce Foxp3(+)CD4(+) regulatory T cells (T-regs) and regulate immunity versus tolerance in the intestines. However, the contribution of DCs to controlling immunity versus tolerance in the oral cavity has not been addressed. Here, we report that DCs from the oral cavity induce Foxp3(+) T-regs as well as DCs from intestine. We found that oral-cavity-draining cervical lymph nodes contained higher frequencies of Foxp3(+) T-regs and ROR-γt(+) CD4(+)T cells than other lymph nodes. The high frequency of Foxp3(+) T-regs in the oral-cavity-draining cervical lymph nodes was not dependent on the Toll like receptor (TLR) adaptor molecules, Myd88 and TICAM-1 (TRIF). In contrast, the high frequency of ROR-γt(+) CD4(+)T cells relies on Myd88 and TICAM-1. In vitro data showed that CD11c(+) DCs from oral-cavity-draining cervical lymph nodes have the capacity to induce Foxp3(+) T-regs in the presence of antigen. These data suggest that, as well as in the intestinal environment, antigen-presenting DCs may play a vital role in maintaining tolerance by inducing Foxp3(+) T-regs in the oral cavity.
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. yamazas@med.nagoya-cu.ac.jp
authors.forename: Sayuri
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Akira
authors.initials: A
authors.lastname: Maruyama
authors.forename: Kohei
authors.initials: K
authors.lastname: Okada
authors.forename: Misako
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Akimichi
authors.initials: A
authors.lastname: Morita
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Seya
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000096:biosynthesis; D000818:Animals; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D007422:Intestines / Q000276:immunology; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009055:Mouth / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000941:Antigens; D016207:Cytokines; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D053594:Myeloid Differentiation Factor 88; C418974:FOXP3 protein, human; C507779:MYD88 protein, human; C476286:Ticam1 protein, mouse