title: The protective effect of the anti-Toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA.
abstract: Toll-like Receptor 9 (TLR9) is an innate immune receptor recognizing microbial DNA. TLR9 is also activated by self-derived DNA, such as mitochondrial DNA, in a variety of inflammatory diseases. We show here that TLR9 activation in vivo is controlled by an anti-TLR9 monoclonal Ab (mAb). A newly established mAb, named NaR9, clearly detects endogenous TLR9 expressed in primary immune cells. The mAb inhibited TLR9-dependent cytokine production in vitro by bone marrow-derived macrophages and conventional dendritic cells. Furthermore, NaR9 treatment rescued mice from fulminant hepatitis caused by administering the TLR9 ligand CpGB and D-(+)-galactosamine. The production of proinflammatory cytokines induced by CpGB and D-(+)-galactosamine was significantly impaired by the mAb. These results suggest that a mAb is a promising tool for therapeutic intervention in TLR9-dependent inflammatory diseases.
authors.affiliation: Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Fukui
authors.affiliation: Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Motoi
authors.affiliation: Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Shin-Ichiroh
authors.initials: SI
authors.lastname: Saitoh
authors.affiliation: Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Sato
authors.affiliation: Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.|Laboratory of Innate Immunity, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miyake
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004247:DNA / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D011992:Endosomes / Q000378:metabolism; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000276:immunology; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020011:Protective Agents / Q000008:administration & dosage*; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D020011:Protective Agents; D051217:Toll-Like Receptor 9; D004247:DNA