title: Release from Th1-type immune tolerance in spleen and enhanced production of IL-5 in Peyer's patch by cholera toxin B induce the glomerular deposition of IgA.
abstract: We examined the pathogenesis of glomerular damage in Th2 type-dependent GATA-3 transgenic (GATA-3 Tg) mice with IgA nephropathy (IgAN). GATA-3 Tg mice were immunized orally using OVA plus cholera toxin B (CTB), and measurement of the serum IgA antibody level and histopathological examination were performed. Marked increases in the serum levels of OVA-specific IgA antibody, IgA and IgG, C3 deposits analogous to those seen in IgAN, and expansion of the matrix in association with mesangial cell proliferation were observed. Furthermore, glomerular IgA deposits were co-localized with mannan-binding lectin (MBL) deposits, which might actually have been abnormal IgA deposits. In GATA-3/TCR-Tg mice that had been orally sensitized with CTB plus OVA and were re-stimulated with OVA in vitro, cultured Peyer's patch cells showed the enhanced production of IL-5 and supernatants from cultures of spleen cells showed a reduction of TGF-β production with a simultaneous increase in IL-2 production and the recovery of IFN-γ formation. The amount of TGF-β produced by the spleen cells was found to be correlated with the amount of IFN-γ and IL-IL-2 produced by the cells. Also, the percentage of regulatory T cells (Treg) in the spleens of mice sensitized with OVA plus CTB was lower than that in mice orally sensitized with OVA alone. These results suggest that the increased production of IL-5 from Peyer's patch cells (PPc) and the restored Th1-type immune response might cause the production of abnormal IgA and might induce the deposition of IgA in glomeruli.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamanaka
authors.affiliation: Division of Cellular Immunology, Kitasato University Graduate School of Medical Science, Kitasato, 1-15-1, Minami, Sagamihara, Kanagawa 252-0373, Japan; Division of Fundamental Medical Technology, Department of Immunology, Ehime Prefecture University of Health Sciences, Takooda 543, Tobe-cho, Iyo-gun, Ehime 791-2101, Japan. Electronic address: hidetama@epu.ac.jp.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tamauchi
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Horikoshi
authors.affiliation: Ehime Plant, Dainippon Sumitomo Pharma Co., Ltd., Sobiraki-cho, Niihama, Ehime 792-0001, Japan.
authors.forename: Masazumi
authors.initials: M
authors.lastname: Terashima
authors.affiliation: Division of Cellular Immunology, Kitasato University Graduate School of Medical Science, Kitasato, 1-15-1, Minami, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwabuchi
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Sonoko
authors.initials: S
authors.lastname: Habu
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology*; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D005922:Glomerulonephritis, IGA / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology*; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000276:immunology; D050527:Mesangial Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010581:Peyer's Patches / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D061251:Primary Cell Culture; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D007070:Immunoglobulin A; D015848:Interleukin-5; D037601:Mannose-Binding Lectin; D010047:Ovalbumin; D002772:Cholera Toxin
keywords: GATA-3; IgA deposition; IgA nephropathy; Mucosal immunity; Th1/Th2