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Clin Exp Immunol. 2005 Aug;141(2):230-7.

Modulation of the immune response in pristane-induced lupus by expression of activation and inhibitory Fc receptors.

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1
Department of Medicine and Microbiology, Columbia University, New York, USA.

Abstract

Altered homeostasis in Fcgamma receptor (FcgammaR) expression has been implicated in the induction of both immune complex-mediated glomerulonephritis and autoantibody production in systemic lupus erythematosus. FcgammaRI and III are required for immune complexes to activate inflammatory cells, thereby inciting tissue injury. In contrast, FcgammaRIIB functions as a negative regulator of immune complex-mediated inflammation and autoantibody production. We investigated the role of FcgammaRI/III versus FcgammaRIIB on pristane-induced lupus in mice. FcgammaRI/III and FcgammaRIIB-deficient ((-/-)) and control ((+/+)) BALB/c mice were injected with either pristane or PBS. Proteinuria and glomerular immune deposits were evaluated 9 months after treatment and serial sera were analysed for total IgG levels and lupus-specific autoantibodies. The incidence of nephritis was higher in pristane-treated FcgammaRIIB(-/-) mice than pristane-treated FcgammaRI/III(-/-) and (+/+) mice. Hypergammaglobulinaemia and spontaneous anti-DNA/chromatin autoantibody production were associated with interleukin (IL)-6 over-expression in FcgammaRIIB(-/-) mice and were augmented further by pristane treatment when compared to both FcgammaRI/III(-/-) and (+/+) mice. Lack of either FcgammaRIIB or FcgammaRI/III had little effect on both anti-nRNP/Sm and anti-Su production induced by pristane. Our results confirm that spontaneous autoimmunity occurs in the absence of FcgammaRIIB. Moreover, the lupus-like syndrome induced by pristane in BALB/c mice was regulated by opposing activating and inhibitory FcgammaRs. Activating FcgammaRs were required for significant proteinuria and unbridled activation in the absence of FcgammaRIIB dramatically exacerbated glomerular inflammatory responses. FcgammaRIIB may be a key modulator that suppresses cell activation in the inflammatory immune response in systemic lupus erythematosus in humans.

PMID:
15996187
PMCID:
PMC1809443
DOI:
10.1111/j.1365-2249.2005.02847.x
[Indexed for MEDLINE]
Free PMC Article
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