title: Breakdown of mucosal immunity in the gut and resultant systemic sensitization by oral antigens in a murine model for systemic lupus erythematosus.
abstract: Secreted IgA plays a pivotal role in the mucosal immunity to maintain the front line of body defense. We found that the level of fecal IgA was dramatically decreased in aged (NZB x NZW)F(1) (BWF(1)) mice developing lupus nephritis, whereas levels in similarly aged New Zealand Black (NZB) and New Zealand White (NZW) mice remained unchanged compared with young mice. The number of cells obtained from Peyer's patches was markedly decreased in aged BWF(1) mice. Aged BWF(1) mice showed increased susceptibility to pathogenic bacterial infection. Furthermore, oral administration of OVA failed to inhibit secondary IgG response induced by systemic immunization, suggesting defective oral tolerance in aged BWF(1) mice. A significant amount of orally administered OVA was incorporated directly into the intestinal lamina propria in aged BWF(1) mice whereas it was mainly localized in subepithelial domes and interfollicular region in Peyer's patches in young mice. T cells obtained from renal and pulmonary lymph nodes of aged BWF(1) mice that had been orally administered with OVA showed an Ag-specific T cell proliferation, whereas those from young BWF(1), aged NZB, and aged NZW mice did not. Interestingly, aerosol exposure to OVA of aged BWF(1) mice, which had been orally administered with the same Ag, provoked an eosinophil infiltration in the lung. These results demonstrate that mucosal immunity in the gut is impaired and oral Ags induce systemic sensitization instead of oral tolerance in the development of murine lupus.
authors.affiliation: Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Akadegawa
authors.forename: Sho
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Taku
authors.initials: T
authors.lastname: Sato
authors.forename: Jun
authors.initials: J
authors.lastname: Suzuki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yurino
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kitabatake
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kuriyama
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D003433:Crosses, Genetic; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology; D004927:Escherichia coli Infections / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006834:Hydrazines / Q000378:metabolism; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism
chemical_list: C417561:Alexa 488 hydrazide; D000941:Antigens; D006834:Hydrazines; D007070:Immunoglobulin A; D010047:Ovalbumin