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 and Hiroshi Takayanagi ()
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Takako Negishi-Koga: Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
Hans-Jürgen Gober: Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
Eriko Sumiya: Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
Noriko Komatsu: Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
Kazuo Okamoto: Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
Shinichiro Sawa: Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
Ayako Suematsu: Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
Tomomi Suda: Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
Kojiro Sato: Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
Toshiyuki Takai: Institute of Development, Aging, and Cancer, Tohoku University
Hiroshi Takayanagi: Graduate School of Medicine and Faculty of Medicine, The University of Tokyo

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7637

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