Mediation of nonerosive arthritis in a mouse model of lupus by interferon-alpha-stimulated monocyte differentiation that is nonpermissive of osteoclastogenesis.

OBJECTIVE

In contrast to rheumatoid arthritis (RA), the joint inflammation referred to as Jaccoud's arthritis that occurs in systemic lupus erythematosus (SLE) is nonerosive. Although the mechanism responsible is unknown, the antiosteoclastogenic cytokine interferon-alpha (IFNalpha), whose transcriptome is present in SLE monocytes, may be responsible. This study was undertaken to examine the effects of IFNalpha and lupus on osteoclasts and erosion in the (NZB x NZW)F(1) mouse model of SLE with K/BxN serum-induced arthritis.

METHODS

Systemic IFNalpha levels in (NZB x NZW)F(1) mice were elevated by administration of AdIFNalpha. SLE disease was marked by anti-double-stranded DNA (anti-dsDNA) antibody titer and proteinuria, and Ifi202 and Mx1 expression represented the IFNalpha transcriptome. Microfocal computed tomography was used to evaluate bone erosions. Flow cytometry for CD11b and CD11c was used to evaluate the frequency of circulating osteoclast precursors (OCPs) and myeloid dendritic cells (DCs) in blood.

RESULTS

Administration of AdIFNalpha to (NZB x NZW)F(1) mice induced osteopetrosis. (NZB x NZW)F(1) mice without autoimmune disease were fully susceptible to focal erosions in the setting of serum-induced arthritis. However, (NZB x NZW)F(1) mice with high anti-dsDNA antibody titers and the IFNalpha transcriptome were protected against bone erosions. AdIFNalpha pretreatment of NZW mice before K/BxN serum administration also resulted in protection against bone erosion (r(2) = 0.4720, P < 0.01), which was associated with a decrease in the frequency of circulating CD11b+CD11c- OCPs and a concomitant increase in the percentage of CD11b+CD11c+ cells (r(2) = 0.6330, P < 0.05), which are phenotypic of myeloid DCs.

CONCLUSION

These findings suggest that IFNalpha in SLE shifts monocyte development toward myeloid DCs at the expense of osteoclastogenesis, thereby resulting in decreased bone erosion.