title: Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases.
abstract: Toll-like receptor 7 (TLR7) senses microbial-derived RNA but can also potentially respond to self-derived RNA. To prevent autoimmune responses, TLR7 is thought to localize in endolysosomes. Contrary to this view, we show here that TLR7 is present on the cell surface of immune cells and that TLR7 responses can be inhibited by an anti-TLR7 antibody. The anti-TLR7 antibody is internalized with TLR7 and accumulates in endolysosomes as an immune complex. TLR7 responses in dendritic cells, macrophages and B cells are all inhibited by the anti-TLR7 antibody. Furthermore, the anti-TLR7 antibody inhibits in vivo cytokine production induced by a TLR7 ligand. Spontaneous TLR7 activation in Unc93b1(D34A/D34A) mice causes lethal inflammation. Progressive inflammation such as splenomegaly, thrombocytopenia and chronic active hepatitis are ameliorated by anti-TLR7 antibody treatment. These results demonstrate that cell surface TLR7 is a promising target for therapeutic intervention in autoimmune diseases.
authors: 1] Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108 8639, Japan [2] Laboratory of Innate Immunity, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108 8639, Japan.
authors: Atsuo
authors: A
authors: Kanno
authors: 1] Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108 8639, Japan [2] Japan Society for the Promotion of Science, 5-3-1, Kojimachi, Chiyodaku, Tokyo 102 0083, Japan.
authors: Natsuko
authors: N
authors: Tanimura
authors: Daiichi Sankyo Shinagawa R&D center, Daiichi Sankyo Co. Ltd., 1-chome, Hiromachi, Tokyo 140 8710, Japan.
authors: Masayuki
authors: M
authors: Ishizaki
authors: Department of Dermatology, Kochi Medical School, Kochi University, Kohasu, Okocho, Nankoku 783 8505, Japan.
authors: Kentaro
authors: K
authors: Ohko
authors: Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108 8639, Japan.
authors: Yuji
authors: Y
authors: Motoi
authors: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700 8558, Japan.
authors: Masahiro
authors: M
authors: Onji
authors: Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108 8639, Japan.
authors: Ryutaro
authors: R
authors: Fukui
authors: Daiichi Sankyo Shinagawa R&D center, Daiichi Sankyo Co. Ltd., 1-chome, Hiromachi, Tokyo 140 8710, Japan.
authors: Takaichi
authors: T
authors: Shimozato
authors: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700 8558, Japan.
authors: Kazuhide
authors: K
authors: Yamamoto
authors: 1] Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108 8639, Japan [2] CREST, Japan Science and Technology Agency, 4-1-8, Honcho, Kawaguchi-shi, Saitama 332 0012, Japan.
authors: Takuma
authors: T
authors: Shibata
authors: Department of Dermatology, Kochi Medical School, Kochi University, Kohasu, Okocho, Nankoku 783 8505, Japan.
authors: Shigetoshi
authors: S
authors: Sano
authors: Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo 4-1, Sendai 980 8575, Japan.
authors: Akiko
authors: A
authors: Sugahara-Tobinai
authors: Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo 4-1, Sendai 980 8575, Japan.
authors: Toshiyuki
authors: T
authors: Takai
authors: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113 0033, Japan.
authors: Umeharu
authors: U
authors: Ohto
authors: 1] CREST, Japan Science and Technology Agency, 4-1-8, Honcho, Kawaguchi-shi, Saitama 332 0012, Japan [2] Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113 0033, Japan.
authors: Toshiyuki
authors: T
authors: Shimizu
authors: Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108 8639, Japan.
authors: Shin-ichiroh
authors: S
authors: Saitoh
authors: 1] Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108 8639, Japan [2] Laboratory of Innate Immunity, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108 8639, Japan.
authors: Kensuke
authors: K
authors: Miyake