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[PROVISIONAL] There is currently no paradigm to explain how the immune system can mount distinct responses to different types of immunological threat. Here we show that different types of immunity induced by a class of inorganic crystalline materials are driven purely by their physicochemical characteristics, in a highly predictable manner. We show that layered double hydroxides (LDHs) can elicit diverse responses of human dendritic cells (DC) in vitro, and antigen-specific mouse antibody responses in vivo. Using a systems vaccinology approach we prove that the magnitude of every response studied is precisely determined by a subset of just three physical and chemical properties, for all compounds tested. To assess the robustness of this ‘chemical-immunology rule’ we confirm that multiple DC responses to newly-synthesised compounds can be predicted with exceptional accuracy from a measurement of only these parameters. We also show that inflammatory responses of human macrophages in vitro are controlled by the same rules, suggesting they may apply at both the individual component and global levels of immunity. This study demonstrates that immunity can be driven purely by chemistry, and opens the possibility of rational manipulation of immunity for therapeutic purposes.


Journal article


Nature Medicine

Publication Date