CD47 deficiency ameliorates autoimmune nephritis in Fas(lpr) mice by suppressing IgG autoantibody production.

Abstract

CD47, a self-recognition marker, plays an important role in both innate and adaptive immune responses. To explore the potential role of CD47 in activation of autoreactive T and B cells and the production of autoantibodies in autoimmune disease, especially systemic lupus erythematosus (SLE), we have generated CD47 knockout Fas(lpr) (CD47(-/-) -Fas(lpr) ) mice and examined histopathological changes in the kidneys, cumulative survival rates, proteinuria, extent of splenomegaly and autoantibodies, serum chemistry and immunological parameters. In comparison with Fas(lpr) mice, CD47(-/-) -Fas(lpr) mice exhibit a prolonged lifespan and delayed autoimmune nephritis, including glomerular cell proliferation, basement membrane thickening, acute tubular atrophy and vacuolization. CD47(-/-) -Fas(lpr) mice have lower levels of proteinuria, associated with reduced deposition of complement C3 and C1q, and IgG but not IgM in the glomeruli, compared to age-matched Fas(lpr) mice. Serum levels of antinuclear antibodies and anti-double-stranded DNA antibodies are significantly lower in CD47(-/-) -Fas(lpr) than in Fas(lpr) mice. CD47(-/-) -Fas(lpr) mice also display less pronounced splenomegaly than Fas(lpr) mice. The mechanistic studies further suggest that CD47 deficiency impairs the antigenic challenge-induced production of IgG but not IgM, and that this effect is associated with reduction of T follicular cells and impairment of germinal centre development in lymphoid tissues. In conclusion, our results demonstrate that CD47 deficiency ameliorates lupus nephritis in Fas(lpr) mice via suppression of IgG autoantibody production.

• Authors: Lei Shi, Zhen Bian, Celia X J Chen, Ya-Nan Guo, Zhiyuan Lv, Caihong Zeng, Zhihong Liu, Ke Zen, Yuan Liu
• Journal: The Journal of pathology (J Pathol) Vol. 237 Issue 3 Pg. 285-95 (Nov 2015) ISSN: 1096-9896 [Electronic] England
• PMID: 26095930 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Chemical References

• Antibodies, Antinuclear
• CD47 Antigen
• Cd47 protein, mouse
• Fas protein, mouse
• Immunoglobulin G
• fas Receptor
• Complement System Proteins

Topics

• Animals
• Antibodies, Antinuclear (biosynthesis, blood, immunology)
• CD47 Antigen (genetics, immunology, metabolism)
• Cell Proliferation
• Complement System Proteins (immunology, metabolism)
• Disease Models, Animal
• Immunoglobulin G (biosynthesis, blood, immunology)
• Kidney Glomerulus (immunology, metabolism, pathology)
• Lupus Nephritis (genetics, immunology, metabolism, pathology, prevention & control)
• Mice, Inbred C57BL
• Mice, Knockout
• Proteinuria (genetics, immunology, metabolism, prevention & control)
• Splenomegaly (genetics, immunology, metabolism, prevention & control)
• T-Lymphocytes, Helper-Inducer (immunology, metabolism)
• Time Factors
• fas Receptor (deficiency, genetics, immunology)