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Immune complexes regulate bone metabolism through FcRγ signalling

Author

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  • Takako Negishi-Koga

    (Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
    Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Program, Takayanagi Osteonetwork Project)

  • 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
    Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Program, Takayanagi Osteonetwork Project)

  • Kazuo Okamoto

    (Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
    Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Program, Takayanagi Osteonetwork Project)

  • Shinichiro Sawa

    (Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
    Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Program, Takayanagi Osteonetwork Project)

  • 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
    Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Program, Takayanagi Osteonetwork Project)

  • Kojiro Sato

    (Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
    Present address: Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Morohongo 38, Moroyama, Iruma-gun, Saitama 350-0495, Japan)

  • Toshiyuki Takai

    (Institute of Development, Aging, and Cancer, Tohoku University)

  • Hiroshi Takayanagi

    (Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
    Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Program, Takayanagi Osteonetwork Project
    Centre for Orthopaedic Research, School of Surgery, The University of Western Australia)

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.

Suggested Citation

  • Takako Negishi-Koga & Hans-Jürgen Gober & Eriko Sumiya & Noriko Komatsu & Kazuo Okamoto & Shinichiro Sawa & Ayako Suematsu & Tomomi Suda & Kojiro Sato & Toshiyuki Takai & Hiroshi Takayanagi, 2015. "Immune complexes regulate bone metabolism through FcRγ signalling," Nature Communications, Nature, vol. 6(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7637
    DOI: 10.1038/ncomms7637
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    Cited by:

    1. Yibo He & Changrong Ge & Àlex Moreno-Giró & Bingze Xu & Christian M. Beusch & Katalin Sandor & Jie Su & Lei Cheng & Erik Lönnblom & Christina Lundqvist & Linda M. Slot & Dongmei Tong & Vilma Urbonavic, 2023. "A subset of antibodies targeting citrullinated proteins confers protection from rheumatoid arthritis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Zhongwei Xu & Bingze Xu & Susanna L. Lundström & Àlex Moreno-Giró & Danxia Zhao & Myriam Martin & Erik Lönnblom & Qixing Li & Alexander Krämer & Changrong Ge & Lei Cheng & Bibo Liang & Dongmei Tong & , 2023. "A subset of type-II collagen-binding antibodies prevents experimental arthritis by inhibiting FCGR3 signaling in neutrophils," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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