title: Critical role of TSLP-responsive mucosal dendritic cells in the induction of nasal antigen-specific IgA response.
abstract: Thymic stromal lymphopoietin (TSLP) is an interleukin-7 (IL-7)-like cytokine involved in T helper 2 type immune responses. The primary target of TSLP is myeloid dendritic cells (DCs), however, little is known about the mechanism by which TSLP elicits respiratory IgA immune responses upon mucosal immunization. Here, we found that the levels of TSLP and TSLPR were upregulated in the mucosal DCs of mice nasally immunized with pneumococcal surface protein A (PspA) plus cholera toxin (CT) compared with those immunized with PspA alone. PspA-specific IgA responses, but not IgG Ab responses were significantly reduced in both serum and mucosal secretions of TSLPR knockout mice compared with wild-type mice after nasal immunization with PspA plus CT. Furthermore, CD11c+mucosal DCs isolated from TSLPR knockout mice nasally immunized with PspA plus CT were less activated and exhibited markedly reduced expression of IgA-enhancing cytokines (e.g., APRIL, BAFF, and IL-6) compared with those from equivalently immunized wild-type mice. Finally, exogenous TSLP promoted production of IgAs in an in vitro DC-B cell co-culture system as exhibited by enhanced IL-6 production. These results suggest that TSLP-TSLPR signaling is pivotal in the induction of nasal respiratory immunity against pathogenic pneumococcal infection.
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.|Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Joo
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuyama
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.|Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: E J
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yuki
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.|Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kurashima
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Ouchida
authors.affiliation: Immunology Program, Benaroya Research Institute, Seattle, Washington, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Ziegler
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.|Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.|International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.|Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D039521:CD11c Antigen / Q000378:metabolism; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000276:immunology*; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D056724:Immunity, Humoral; D007114:Immunization; D007070:Immunoglobulin A / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000473:pathology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D039521:CD11c Antigen; D016207:Cytokines; D007070:Immunoglobulin A; D007136:Immunoglobulins; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse; C051592:pneumococcal surface protein A; D002772:Cholera Toxin; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse