| First Author | Negishi-Koga T | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6637 | PubMed ID | 25824719 |
| Mgi Jnum | J:221858 | Mgi Id | MGI:5641770 |
| Doi | 10.1038/ncomms7637 | Citation | Negishi-Koga T, et al. (2015) Immune complexes regulate bone metabolism through FcRgamma signalling. Nat Commun 6:6637 |
| abstractText | 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 FcRgamma signalling, which is dependent on the relative expression of positive and negative FcgammaRs (FcgammaRI/III/IV and IIB, respectively) as well as the availability of their ligands, ICs. Under physiological conditions, unexpectedly, FcgammaRIII inhibits osteoclastogenesis by depriving other osteoclastogenic Ig-like receptors of FcRgamma. Fcgr2b(-/-) mice lose bone upon the onset of a hypergammaglobulinemia or the administration of IgG1 ICs, which act mainly through FcgammaRIII. The IgG2 IC activates osteoclastogenesis by binding to FcgammaRI and FcgammaRIV, 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. |
