The complex role of Fcgamma receptors in the pathology of arthritis.
Autoantibodies of the IgG class and the immune complexes they form are central players in the pathology of rheumatoid arthritis (RA). Receptors for the Fc part of IgG, FcgammaR constitute one of the main effector mechanisms through which IgG immune complexes exert their action. The different members of the FcgammaR family exhibit extensive structural homology leading to redundancy in ligand specificity and signal transduction. Moreover, the initiation of effector mechanisms by IgG immune complexes can also be mediated by the complement system. This strong redundancy and high degree of complexity hampers a direct in vivo analysis of antibody effector pathways. Over the last decade, mice deficient for different combinations of FcgammaR have been generated by gene targeting. These knockout mice provide excellent tools to define the specific contribution of the different FcgammaR to IgG effector pathways in well-established in vivo mouse models for arthritis. This review will discuss the results of the studies that analyze the role of the different members of the FcgammaR family in murine arthritis models and their implications for our understanding of the human disease.
Boross
Peter
P
Department of Human Genetics, Leiden University Medical Center, Postzone S4-P P.O. Box 9600, 2300 RC, Leiden, The Netherlands, j.s.verbeek@lumc.nl.
Verbeek
J Sjef
JS
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D006801:Humans; D018345:Mice, Knockout; D011951:Receptors, Complement; D011961:Receptors, Fc; D017452:Receptors, IgG / Q000235:genetics
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D011951:Receptors, Complement; D011961:Receptors, Fc; D017452:Receptors, IgG