Immune complexes regulate bone metabolism through FcRγ signalling

Takako Negishi-Koga, Hans Jürgen Gober, Eriko Sumiya, Noriko Komatsu, Kazuo Okamoto, Shinichiro Sawa, Ayako Suematsu, Tomomi Suda, Kojiro Sato, Toshiyuki Takai, Hiroshi Takayanagi

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53 Citations (Scopus)

Abstract

Autoantibody production and immune complex (IC) formation are frequently observed in autoimmune diseases associated with bone loss. However, it has been poorly understood whether ICs regulate bone metabolism directly. Here we show that the level of osteoclastogenesis is determined by the strength of FcRγ signalling, which is dependent on the relative expression of positive and negative FcγRs (FcγRI/III/IV and IIB, respectively) as well as the availability of their ligands, ICs. Under physiological conditions, unexpectedly, FcγRIII inhibits osteoclastogenesis by depriving other osteoclastogenic Ig-like receptors of FcRγ. Fcgr2b-/-mice lose bone upon the onset of a hypergammaglobulinemia or the administration of IgG1 ICs, which act mainly through FcγRIII. The IgG2 IC activates osteoclastogenesis by binding to FcγRI and FcγRIV, which is induced under inflammatory conditions. These results demonstrate a link between the adaptive immunity and bone, suggesting a regulatory role for ICs in bone resorption in general, and not only in inflammatory diseases.

Original languageEnglish
Article number6637
JournalNature communications
Volume6
DOIs
Publication statusPublished - 2015 Mar 31

ASJC Scopus subject areas

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

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    Negishi-Koga, T., Gober, H. J., Sumiya, E., Komatsu, N., Okamoto, K., Sawa, S., Suematsu, A., Suda, T., Sato, K., Takai, T., & Takayanagi, H. (2015). Immune complexes regulate bone metabolism through FcRγ signalling. Nature communications, 6, [6637]. https://doi.org/10.1038/ncomms7637