title: Immunity induced by a broad class of inorganic crystalline materials is directly controlled by their chemistry.
abstract: There is currently no paradigm in immunology that enables an accurate prediction of how the immune system will respond to any given agent. Here we show that the immunological responses induced by members of a broad class of inorganic crystalline materials are controlled purely by their physicochemical properties in a highly predictable manner. We show that structurally and chemically homogeneous layered double hydroxides (LDHs) can elicit diverse human dendritic cell responses in vitro. Using a systems vaccinology approach, we find that every measured response can be modeled using a subset of just three physical and chemical properties for all compounds tested. This correlation can be reduced to a simple linear equation that enables the immunological responses stimulated by newly synthesized LDHs to be predicted in advance from these three parameters alone. We also show that mouse antigen-specific antibody responses in vivo and human macrophage responses in vitro are controlled by the same properties, suggesting they may control diverse responses at both individual component and global levels of immunity. This study demonstrates that immunity can be determined purely by chemistry and opens the possibility of rational manipulation of immunity for therapeutic purposes.
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry; Nuffield Department of Surgical Sciences, John Radcliffe Hospital; and Department of Statistics; University of Oxford, Oxford OX1 2JD, England, UKChemistry Research Laboratory, Department of Chemistry; Nuffield Department of Surgical Sciences, John Radcliffe Hospital; and Department of Statistics; University of Oxford, Oxford OX1 2JD, England, UK.
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Williams
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, Department of Pulmonary Medicine, University Hospital and Flanders Institute for Biotechnology (VIB) Inflammation Research Center, University of Ghent, 9000 Ghent, Belgium Laboratory of Immunoregulation and Mucosal Immunology, Department of Pulmonary Medicine, University Hospital and Flanders Institute for Biotechnology (VIB) Inflammation Research Center, University of Ghent, 9000 Ghent, Belgium.
authors.forename: Kaat
authors.initials: K
authors.lastname: Fierens
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry; Nuffield Department of Surgical Sciences, John Radcliffe Hospital; and Department of Statistics; University of Oxford, Oxford OX1 2JD, England, UK.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Preston
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry; Nuffield Department of Surgical Sciences, John Radcliffe Hospital; and Department of Statistics; University of Oxford, Oxford OX1 2JD, England, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lunn
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry; Nuffield Department of Surgical Sciences, John Radcliffe Hospital; and Department of Statistics; University of Oxford, Oxford OX1 2JD, England, UK.
authors.forename: Oliwia
authors.initials: O
authors.lastname: Rysnik
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, Department of Pulmonary Medicine, University Hospital and Flanders Institute for Biotechnology (VIB) Inflammation Research Center, University of Ghent, 9000 Ghent, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: De Prijck
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, Department of Pulmonary Medicine, University Hospital and Flanders Institute for Biotechnology (VIB) Inflammation Research Center, University of Ghent, 9000 Ghent, Belgium Laboratory of Immunoregulation and Mucosal Immunology, Department of Pulmonary Medicine, University Hospital and Flanders Institute for Biotechnology (VIB) Inflammation Research Center, University of Ghent, 9000 Ghent, Belgium Department of Pulmonary Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Kool
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry; Nuffield Department of Surgical Sciences, John Radcliffe Hospital; and Department of Statistics; University of Oxford, Oxford OX1 2JD, England, UKChemistry Research Laboratory, Department of Chemistry; Nuffield Department of Surgical Sciences, John Radcliffe Hospital; and Department of Statistics; University of Oxford, Oxford OX1 2JD, England, UK.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Buckley
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, Department of Pulmonary Medicine, University Hospital and Flanders Institute for Biotechnology (VIB) Inflammation Research Center, University of Ghent, 9000 Ghent, Belgium Laboratory of Immunoregulation and Mucosal Immunology, Department of Pulmonary Medicine, University Hospital and Flanders Institute for Biotechnology (VIB) Inflammation Research Center, University of Ghent, 9000 Ghent, Belgium Department of Pulmonary Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, Netherlands Bart.Lambrecht@ugent.be.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry; Nuffield Department of Surgical Sciences, John Radcliffe Hospital; and Department of Statistics; University of Oxford, Oxford OX1 2JD, England, UK.
authors.forename: Dermot
authors.initials: D
authors.lastname: O'Hare
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry; Nuffield Department of Surgical Sciences, John Radcliffe Hospital; and Department of Statistics; University of Oxford, Oxford OX1 2JD, England, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Austyn
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D002478:Cells, Cultured; D003460:Crystallization; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006878:Hydroxides / Q000737:chemistry / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D015999:Multivariate Analysis; D010047:Ovalbumin / Q000276:immunology
chemical_list: D000906:Antibodies; D016207:Cytokines; D006878:Hydroxides; D010047:Ovalbumin