Immune complexes regulate bone metabolism through FcRγ signalling

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

Research output: Contribution to journalArticle

46 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 - Mar 31 2015

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metabolism
Antigen-Antibody Complex
Metabolism
bones
Bone
Osteogenesis
Bone and Bones
Immunoglobulin G
Hypergammaglobulinemia
Adaptive Immunity
Bone Resorption
Autoantibodies
Autoimmune Diseases
immunity
availability
mice
Ligands
Availability
ligands

All Science Journal Classification (ASJC) codes

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

Cite this

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

Immune complexes regulate bone metabolism through FcRγ signalling. / Negishi-Koga, Takako; Gober, Hans Jürgen; Matsumoto, Eriko; Komatsu, Noriko; Okamoto, Kazuo; Sawa, Shinichiro; Suematsu, Ayako; Suda, Tomomi; Sato, Kojiro; Takai, Toshiyuki; Takayanagi, Hiroshi.

In: Nature communications, Vol. 6, 6637, 31.03.2015.

Research output: Contribution to journalArticle

Negishi-Koga, T, Gober, HJ, Matsumoto, 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, vol. 6, 6637. https://doi.org/10.1038/ncomms7637
Negishi-Koga, Takako ; Gober, Hans Jürgen ; Matsumoto, Eriko ; Komatsu, Noriko ; Okamoto, Kazuo ; Sawa, Shinichiro ; Suematsu, Ayako ; Suda, Tomomi ; Sato, Kojiro ; Takai, Toshiyuki ; Takayanagi, Hiroshi. / Immune complexes regulate bone metabolism through FcRγ signalling. In: Nature communications. 2015 ; Vol. 6.
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