Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b-/-Pdcd1-/- mice.
Because most autoimmune diseases are polygenic, analysis of the synergistic involvement of various immune regulators is essential for a complete understanding of the molecular pathology of these diseases. We report the regulation of autoimmune diseases by epistatic effects of two immunoinhibitory receptors, low affinity type IIb Fc receptor for IgG (FcgammaRIIB) and programmed cell death 1 (PD-1). Approximately one third of the BALB/c-Fcgr2b(-/-)Pdcd1(-/-) mice developed autoimmune hydronephrosis, which is not observed in either BALB/c-Fcgr2b(-/-) or BALB/c-Pdcd1(-/-) mice. Hydronephrotic mice produced autoantibodies (autoAbs) against urothelial antigens, including uroplakin IIIa, and these antibodies were deposited on the urothelial cells of the urinary bladder. In addition, approximately 15% of the BALB/c-Fcgr2b(-/-)Pdcd1(-/-) mice produced antinuclear autoAbs. In contrast, the frequency of the autoimmune cardiomyopathy and the production of anti-parietal cell autoAb, which were observed in BALB/c-Pdcd1(-/-) mice, were not affected by the additional FcgammaRIIB deficiency. These observations suggest cross talk between two immunoinhibitory receptors, FcgammaRIIB and PD-1, on the regulation of autoimmune diseases.
Okazaki
Taku
T
Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Otaka
Yumi
Y
Wang
Jian
J
Hiai
Hiroshi
H
Takai
Toshiyuki
T
Ravetch
Jeffrey V
JV
Honjo
Tasuku
T
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D004843:Epistasis, Genetic; D006869:Hydronephrosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D061026:Programmed Cell Death 1 Receptor; D020239:Receptor Cross-Talk / Q000276:immunology*; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060171:Uroplakin III
D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D001323:Autoantibodies; C499172:Fcgr2b protein, mouse; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D017452:Receptors, IgG; D060171:Uroplakin III