Ankylosing enthesitis associated with up-regulated IFN-γ and IL-17 production in (BXSB x NZB) F1 male mice: a new mouse model
Ankylosing enthesitis associated with up-regulated IFN-γ and IL-17 production in (BXSB x NZB) F1 male mice: a new mouse model
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DOI：
10.1007/s10165-009-0166-0
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发表时间：
2009-06-01
影响因子：
2.2
通讯作者：
Hirose, Sachiko
中科院分区：
文献类型：
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作者：
Abe, Yasuharu;Ohtsuji, Mareki;Hirose, Sachiko
我们发现，与自发发生严重系统性红斑狼疮（SLE）的（BXSB x NZB）F-1雌性小鼠相反，雄性（BXSB x NZB）F-1小鼠不容易发生SLE，而是仅在分组笼中时在踝关节/跗关节中发生血清阴性强直性附着点炎，7月龄时发生率达到83%。这种关节强直在显微镜下的特征是骨形态发生蛋白（BMP）-2阳性的成纤维细胞样细胞显著增殖，与增生的附着点组织中软骨和骨的异向性形成以及随后的跗骨融合有关。腘淋巴结T细胞产生白细胞介素（IL）-17和干扰素（IFN）-γ的能力升高与关节强直显著相关，表明这些细胞因子参与了疾病的效应期机制，包括上调BMP信号通路。受影响和未受影响的小鼠之间的血清自身抗体水平没有差异。父母BXSB和NZB菌株的两种性别没有发展的疾病，即使在笼子里的群体，表明疾病的发展控制下的易感基因来自父母株。这些结果表明，（BXSB x NZB）F-1雄性小鼠是一个合适的模型，以澄清遗传，环境和分子机制的强直性附着点炎和相关疾病。
We found that in contrast to (BXSB x NZB) F-1 female mice that spontaneously develop severe systemic lupus erythematosus (SLE), male (BXSB x NZB) F-1 mice are not prone to SLE, but instead develop seronegative ankylosing enthesitis in ankle/tarsal joints only when caged in groups, with the incidence reaching 83% at 7 months of age. This ankylosis is microscopically characterized by a marked proliferation of fibroblast-like cells positive for bone morphogenetic protein (BMP)-2 in association with heterotropic formation of cartilages and bones in hyperplastic entheseal tissues and subsequent fusion of tarsal bones. Elevated potentials of popliteal lymph node T cells producing interleukin (IL)-17 and interferon (IFN)-gamma were significantly associated with joint ankylosis, suggesting the involvement of these cytokines in effector phase mechanisms of the disease, including up-regulated BMP signaling pathways. There was no difference in serum autoantibody levels between affected and unaffected mice. Parental BXSB and NZB strains of both sexes did not develop the disease even when caged in groups, indicating that the disease develops under the control of susceptibility genes derived from both parental strains. These results indicate that (BXSB x NZB) F-1 male mice are a suitable model for clarifying genetic, environmental and molecular mechanisms underlying ankylosing enthesitis and related diseases.