title: Amorphous nanosilica particles block induction of oral tolerance in mice.
abstract: The mucosal immune system is exposed to non-self antigens in food and the gut microbiota. Therefore, the recognition of orally ingested non-self antigens is suppressed in healthy individuals to avoid excessive immune responses in a process called "oral tolerance". The breakdown of oral tolerance has been cited as a possible cause of food allergy, and amorphous silica nanoparticles (nSP) have been implicated in this breakdown. As nSP are widely used in foodstuffs and other products, exposure to them is increasing; thus, investigations of any effects of nSP on oral tolerance are urgent. This study evaluated the effects of nSP30 (particle diameter = 39 nm) on immunological unresponsiveness induced in mice with oral ovalbumin (OVA). Specifically, production of OVA-specific antibodies, splenocyte proliferation in response to OVA, and effects on T-helper (TH)-1, TH2, and TH17 responses (in terms of cytokine and IgG/IgE subclass expression) were evaluated. nSP30 increased the levels of OVA-specific IgG in OVA-tolerized mice and induced the proliferation of OVA-immunized splenocytes in response to OVA in a dose-related manner. nSP30 also increased the expression of OVA-specific IgG1, IgE, and IgG2a, indicating stimulation of the TH1 and TH2 responses. The expression of interferon (IFN)-γ (TH1), interleukin (IL)-4 and IL-5 (TH2), and IL-17 (TH17) was also stimulated in a dose-related manner by nSP30 in splenocytes stimulated ex vivo with OVA. The induction of tolerance by OVA, the production of anti-OVA IgG antibodies, and proliferation of splenocytes in response to OVA was inhibited by nSP30 in conjunction with OVA and was dose-related. The nSP30 enhanced TH1 and TH2 responses that might prevent the induction of oral tolerance. Overall, this study showed that the abrogation of OVA-induced oral tolerance in mice by exposure to nSP30 was dose-related and that nSP30 stimulated TH1, TH2, and TH17 responses.
authors.affiliation: a Department of Pharmacology , Kobe Pharmaceutical University , Kobe , Japan ;|b Drug Developmental Research Laboratories , Shionogi & Co., Ltd. , Osaka , Japan.
authors.forename: Tsuguto
authors.initials: T
authors.lastname: Toda
authors.affiliation: a Department of Pharmacology , Kobe Pharmaceutical University , Kobe , Japan ;
authors.forename: Shin
authors.initials: S
authors.lastname: Yoshino
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000276:immunology; D049109:Cell Proliferation; D005512:Food Hypersensitivity / Q000276:immunology*; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D045663:Quantum Dots / Q000706:statistics & numerical data*; D012822:Silicon Dioxide / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000941:Antigens; D007074:Immunoglobulin G; D012822:Silicon Dioxide
keywords: Amorphous silica; nanomaterial; oral tolerance