CD47 deficiency ameliorates autoimmune nephritis in Faslpr mice by suppressing IgG autoantibody production

E-ISSN： 1555-2039|237|3|285-295

ISSN： 0022-3417

Source： THE JOURNAL OF PATHOLOGY, Vol.237, Iss.3, 2015-11, pp. : 285-295

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Abstract

AbstractCD47, 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 Faslpr (CD47−/−−Faslpr) 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 Faslpr mice, CD47−/−−Faslpr mice exhibit a prolonged lifespan and delayed autoimmune nephritis, including glomerular cell proliferation, basement membrane thickening, acute tubular atrophy and vacuolization. CD47−/−−Faslpr 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 Faslpr mice. Serum levels of antinuclear antibodies and anti‐double‐stranded DNA antibodies are significantly lower in CD47−/−−Faslpr than in Faslpr mice. CD47−/−–Faslpr mice also display less pronounced splenomegaly than Faslpr 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 Faslpr mice via suppression of IgG autoantibody production. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.