Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases

Atsuo Kanno, Natsuko Tanimura, Masayuki Ishizaki, Kentaro Ohko, Yuji Motoi, Masahiro Onji, Ryutaro Fukui, Takaichi Shimozato, Kazuhide Yamamoto, Takuma Shibata, Shigetoshi Sano, Akiko Sugahara-Tobinai, Toshiyuki Takai, Umeharu Ohto, Toshiyuki Shimizu, Shin Ichiroh Saitoh, Kensuke Miyake

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

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.

Original languageEnglish
Article number6119
JournalNature communications
Volume6
DOIs
Publication statusPublished - 2015 Feb 4

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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