title: SCARB2/LIMP-2 Regulates IFN Production of Plasmacytoid Dendritic Cells by Mediating Endosomal Translocation of TLR9 and Nuclear Translocation of IRF7.
abstract: Scavenger receptor class B, member 2 (SCARB2) is essential for endosome biogenesis and reorganization and serves as a receptor for both β-glucocerebrosidase and enterovirus 71. However, little is known about its function in innate immune cells. In this study, we show that, among human peripheral blood cells, SCARB2 is most highly expressed in plasmacytoid dendritic cells (pDCs), and its expression is further upregulated by CpG oligodeoxynucleotide stimulation. Knockdown of SCARB2 in pDC cell line GEN2.2 dramatically reduces CpG-induced type I IFN production. Detailed studies reveal that SCARB2 localizes in late endosome/lysosome of pDCs, and knockdown of SCARB2 does not affect CpG oligodeoxynucleotide uptake but results in the retention of TLR9 in the endoplasmic reticulum and an impaired nuclear translocation of IFN regulatory factor 7. The IFN-I production by TLR7 ligand stimulation is also impaired by SCARB2 knockdown. However, SCARB2 is not essential for influenza virus or HSV-induced IFN-I production. These findings suggest that SCARB2 regulates TLR9-dependent IFN-I production of pDCs by mediating endosomal translocation of TLR9 and nuclear translocation of IFN regulatory factor 7.
authors: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, BJ 100101, China; University of Chinese Academy of Sciences, Beijing, BJ 100080, China;
authors: Hao
authors: H
authors: Guo
authors: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, BJ 100101, China;
authors: Jialong
authors: J
authors: Zhang
authors: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, BJ 100101, China; University of Chinese Academy of Sciences, Beijing, BJ 100080, China;
authors: Xuyuan
authors: X
authors: Zhang
authors: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, BJ 100101, China;
authors: Yanbing
authors: Y
authors: Wang
authors: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, BJ 100101, China; University of Chinese Academy of Sciences, Beijing, BJ 100080, China;
authors: Haisheng
authors: H
authors: Yu
authors: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, BJ 100101, China; University of Chinese Academy of Sciences, Beijing, BJ 100080, China;
authors: Xiangyun
authors: X
authors: Yin
authors: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, BJ 100101, China; University of Chinese Academy of Sciences, Beijing, BJ 100080, China;
authors: Jingyun
authors: J
authors: Li
authors: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, BJ 100101, China;
authors: Peishuang
authors: P
authors: Du
authors: Department of Research and Development, Etablissement Français du Sang Rhône-Alpes Grenoble, La Tronche 38701, France;
authors: Joel
authors: J
authors: Plumas
authors: Department of Research and Development, Etablissement Français du Sang Rhône-Alpes Grenoble, La Tronche 38701, France;
authors: Laurence
authors: L
authors: Chaperot
authors: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, BJ 100101, China; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors: Jianzhu
authors: J
authors: Chen
authors: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, BJ 100101, China; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; and.
authors: Lishan
authors: L
authors: Su
authors: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, BJ 100101, China; Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204.
authors: Yongjun
authors: Y
authors: Liu
authors: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, BJ 100101, China; liguozhang@ibp.ac.cn.
authors: Liguo
authors: L
authors: Zhang
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism*; D007370:Interferon Type I / Q000096:biosynthesis*; D051907:Lysosomal Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D051116:Receptors, Scavenger / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D051907:Lysosomal Membrane Proteins; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9