Development and functional evaluation of Th2-biased CD1d ligands containing modified lipid moiety

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  • Nabika Etsuko
    Department of Chemistry, Faculty of Science and Technology, Keio University
  • Kashiwabara Emi
    Department of Chemistry, Faculty of Science and Technology, Keio University
  • Hirata Natsumi
    Department of Chemistry, Faculty of Science and Technology, Keio University
  • Inuki Shinsuke
    Department of Chemistry, Faculty of Science and Technology, Keio University Graduate School of Pharmaceutical Sciences, Kyoto University
  • Fujimoto Yukari
    Department of Chemistry, Faculty of Science and Technology, Keio University

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  • Th2バイアス型脂質改変CD1dリガンド開発と機能解析

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<p> CD1d, one of the lipid antigen-presenting proteins, binds to a glycolipid ligand and forms CD1d-ligand complex, which is recognized by NKT cells and induces the secretion of various cytokines including Th1 and Th2 cytokines. The cytokines are known to control immune responses : Th1 cytokines (e. g. IFN-γ) are involved in cell-mediated immunity such as tumor clearance and protection against infection, and Th2 cytokines (e. g. IL-4) are associated with humoral immunity such as allergies and promotion of antibody production. Recent studies revealed that the balance of the cytokines released by NKT cells depends on the CD1d ligand structures. α-GalCer (KRN7000) is a representative ligand and has potent activity to induce both Th1 and Th2 cytokines. On the other hand, OCH is known as a Th2-selective CD1d ligand, and several clinical trials for the ligand in patients with multiple sclerosis and Crohn's disease are ongoing. However, few studies of potent Th2-selective CD1d ligands have been reported compared with Th1-selective ones, and the detailed mechanism of cytokine balance regulation remains unclear. Therefore, the development of potent Th2-selective ligands and elucidation of their biasing mechanism are required. In this article, we review the reported Th2-biased CD1d ligands and the cellular imaging with Th2-biased lipid-modified CD1d ligands for understanding of Th1/Th2 selectivity.</p>

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