title: Immunomodulation and T helper TH₁/TH₂ response polarization by CeO₂ and TiO₂ nanoparticles.
abstract: Immunomodulation by nanoparticles, especially as related to the biochemical properties of these unique materials, has scarcely been explored. In an in vitro model of human immunity, we demonstrate two catalytic nanoparticles, TiO₂ (oxidant) and CeO₂ (antioxidant), have nearly opposite effects on human dendritic cells and T helper (T(H)) cells. For example, whereas TiO₂ nanoparticles potentiated DC maturation that led towards T(H)1-biased responses, treatment with antioxidant CeO₂ nanoparticles induced APCs to secrete the anti-inflammatory cytokine, IL-10, and induce a T(H)2-dominated T cell profile. In subsequent studies, we demonstrate these results are likely explained by the disparate capacities of the nanoparticles to modulate ROS, since TiO₂, but not CeO₂ NPs, induced inflammatory responses through an ROS/inflammasome/IL-1β pathway. This novel capacity of metallic NPs to regulate innate and adaptive immunity in profoundly different directions via their ability to modulate dendritic cell function has strong implications for human health since unintentional exposure to these materials is common in modern societies.
authors.affiliation: Sanofi Pasteur, VaxDesign Campus, Orlando, Florida, United States of America.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Schanen
authors.forename: Soumen
authors.initials: S
authors.lastname: Das
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Reilly
authors.forename: William L
authors.initials: WL
authors.lastname: Warren
authors.forename: William T
authors.initials: WT
authors.lastname: Self
authors.forename: Sudipta
authors.initials: S
authors.lastname: Seal
authors.forename: Donald R
authors.initials: DR
authors.lastname: Drake
mesh_terms: D000704:Analysis of Variance; D002384:Catalysis; D049109:Cell Proliferation; D002563:Cerium / Q000276:immunology* / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D005453:Fluorescence; D006801:Humans; D056747:Immunomodulation / Q000502:physiology*; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism; D053768:Metal Nanoparticles; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D014025:Titanium / Q000276:immunology* / Q000494:pharmacology
chemical_list: D058847:Inflammasomes; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D002563:Cerium; C030583:ceric oxide; D014025:Titanium