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.
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.
J Exp Med. 2014 Jun 2;211(6):1019-25. doi: 10.1084/jem.20131768. Epub 2014 May 5.
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.
目前，免疫学中还没有一种范式能够准确预测免疫系统对任何给定物质的反应。在这里，我们表明，广泛的无机晶体材料类别中的成员所引起的免疫反应仅通过其物理化学性质以高度可预测的方式控制。我们表明，结构和化学均一的层状双氢氧化物（LDH）可以在体外诱导体人树突状细胞的多种反应。使用系统疫苗学方法，我们发现对于所有测试的化合物，仅使用三个物理和化学性质的子集就可以对每个测量的反应进行建模。这种相关性可以简化为一个简单的线性方程，仅从这三个参数就可以预测新合成的 LDH 刺激的免疫反应。我们还表明，体内的小鼠抗原特异性抗体反应和体外的人巨噬细胞反应受相同性质控制，这表明它们可能控制个体成分和整体免疫水平的各种反应。这项研究表明，免疫可以完全由化学决定，并为治疗目的合理操纵免疫开辟了可能性。
