在狼疮小鼠模型中，通过干扰素-α刺激的单核细胞分化介导非侵蚀性关节炎，这种分化不允许破骨细胞生成。
Mediation of nonerosive arthritis in a mouse model of lupus by interferon-alpha-stimulated monocyte differentiation that is nonpermissive of osteoclastogenesis.
作者信息
Mensah Kofi A, Mathian Alexis, Ma Lin, Xing Lianping, Ritchlin Christopher T, Schwarz Edward M
机构信息
University of Rochester Medical Center and University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
出版信息
Arthritis Rheum. 2010 Apr;62(4):1127-37. doi: 10.1002/art.27312.
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.
目的
与类风湿关节炎（RA）不同，系统性红斑狼疮（SLE）中出现的被称为雅库病关节炎的关节炎症是非侵蚀性的。尽管其发病机制尚不清楚，但抗破骨细胞生成细胞因子α干扰素（IFNα）可能与之有关，该因子的转录组存在于SLE单核细胞中。本研究旨在探讨IFNα和狼疮对（NZB×NZW）F1小鼠模型（伴有K/BxN血清诱导性关节炎的SLE模型）中破骨细胞和骨侵蚀的影响。
方法
通过给予AdIFNα提高（NZB×NZW）F1小鼠的全身IFNα水平。SLE疾病以抗双链DNA（抗dsDNA）抗体滴度和蛋白尿为标志，Ifi202和Mx1表达代表IFNα转录组。使用微焦点计算机断层扫描评估骨侵蚀情况。采用流式细胞术检测CD11b和CD11c，以评估血液中循环破骨细胞前体（OCPs）和髓样树突状细胞（DCs）的频率。
结果
给（NZB×NZW）F1小鼠注射AdIFNα可诱导骨质石化。无自身免疫性疾病的（NZB×NZW）F1小鼠在血清诱导性关节炎情况下对局部侵蚀完全敏感。然而，抗dsDNA抗体滴度高且具有IFNα转录组的（NZB×NZW）F1小鼠可免受骨侵蚀。在给予K/BxN血清前对NZW小鼠进行AdIFNα预处理也可防止骨侵蚀（r2 = 0.4720，P < 0.01），这与循环中CD11b + CD11c - OCPs频率降低以及CD11b + CD11c +细胞百分比相应增加有关（r2 = 0.6330，P < 0.05），CD11b + CD11c +细胞是髓样DCs的表型。
结论
这些发现表明，SLE中的IFNα使单核细胞发育向髓样DCs偏移，以破骨细胞生成为代价，从而导致骨侵蚀减少。
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