title: Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance.
abstract: Oral tolerance prevents pathological inflammatory responses to innocuous foreign antigens by peripheral regulatory T cells (pT(reg) cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure for the 'instruction' of naive CD4(+) T cells to differentiate into pT(reg) cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs were dispensable, while classical dendritic cells (cDCs) were critical, for pT(reg) cell induction and oral tolerance. CD11b(-) cDCs from the gut-draining lymph nodes efficiently induced pT(reg) cells and, conversely, loss of transcription factor IRF8-dependent CD11b(-) cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in the induction of pT(reg) cells and their redundancy during the development of oral tolerance.
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Daria
authors.initials: D
authors.lastname: Esterházy
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Jakob
authors.initials: J
authors.lastname: Loschko
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Mariya
authors.initials: M
authors.lastname: London
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Veronica
authors.initials: V
authors.lastname: Jove
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Thiago Y
authors.initials: TY
authors.lastname: Oliveira
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Daniel
authors.identifier: http://orcid.org/0000-0002-0000-0452
authors.initials: D
authors.lastname: Mucida
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000276:immunology*; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004032:Diet; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology*; D007114:Immunization / Q000379:methods; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D000099185:Interferon Regulatory Factor-8
chemical_list: D000941:Antigens; D039481:CD11b Antigen; D050835:Interferon Regulatory Factors; D000099185:Interferon Regulatory Factor-8