Immune complexes regulate bone metabolism through FcRγ signalling.

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.

• Authors: Takako Negishi-Koga, Hans-Jürgen Gober, Eriko Sumiya, Noriko Komatsu, Kazuo Okamoto, Shinichiro Sawa, Ayako Suematsu, Tomomi Suda, Kojiro Sato, Toshiyuki Takai, Hiroshi Takayanagi
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 6637 (Mar 31 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 25824719 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigen-Antibody Complex
• Autoantibodies
• Fcgr1 protein, mouse
• Fcgr2b protein, mouse
• Fcgr3 protein, mouse
• Fcgr4 protein, mouse
• Immunoglobulin G
• Receptors, IgG

Topics

• Animals
• Antigen-Antibody Complex (immunology, metabolism)
• Autoantibodies (immunology)
• Autoimmune Diseases (immunology)
• Bone Resorption (genetics, immunology)
• Bone and Bones (immunology, metabolism)
• Hypergammaglobulinemia (immunology, metabolism)
• Immunoglobulin G (immunology)
• Mice
• Mice, Knockout
• Osteoclasts (metabolism)
• Receptors, IgG (genetics, immunology, metabolism)