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首页> 外文期刊>Arthritis and Rheumatism >The enigmatic role of interleukin-12 in the pathogenesis of Sj?gren's syndrome: Comment on the article by Vosters et al
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The enigmatic role of interleukin-12 in the pathogenesis of Sj?gren's syndrome: Comment on the article by Vosters et al

机译：白细胞介素12在干燥综合征的发病机理中的神秘作用：评论Vosters等人的文章

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To the Editor:Vosters et al (1) recently reported that autoimmunity-prone interleukin-12 (IL-12)-transgenic mice represent a new model of Sjogren's syndrome (SS) (1). IL-12-transgenic animals were generated by expressing the biologically active IL-12 p70 heterodimer under the control of the thyroglobulin promoter. The mice exhibited high serum levels of EL-12, and IL-Independent lymphocytic infiltration of the thyroid, the lungs, and the salivary and the lacrimal glands, mimicking human SS (2). Vosters and colleagues demonstrated that salivary flow was reduced in IL-12-transgenic mice compared with wild-type controls. Salivary glands showed increased lymphocytic infiltration with reduced numbers of acini, and serum anti-SSB/La antibodies (a serologic hallmark of SS [3]) were consistently detected, together with antinuclear antibodies (ANAs).IL-12 binds to a heterodimeric receptor (IL-12R) composed of the j81 and j32 chains. IL-12R/31 is also a component of the receptor for IL-23, an IL-12-related cyto-kine, whereas IL-12R/32 is exclusively a chain of the IL-12R. A few years ago, in the context of studies on the role of IL-12R|82 in B cell lymphoproliferative disorders (4), we investigated whether C57BL/6J//-12rb2-knockout (KO) mice, which produce IL-12 but cannot utilize it, spontaneously developed lymphoproliferative disorders or immune dysregula-tion (5). These mice, starting at the age of 4 months, manifested subclinical multiorgan lymphoid infiltration involving kidneys, liver, lungs, and salivary glands; this finding increased with age and was completely absent in wild-type mice. The infiltrates had a periarteriolar distribution featuring systemic vasculitis and were often organized into ectopic lymphoid follicle-like structures that formed close to peripheral node addressin-positive vessels, contained a core of activated B cells intermingled with follicular dendritic cells, and were bordered by small mature T lymphocytes (5). Interestingly, parotid and submaxillary glands of Il-12rb2-KO mice could also develop lymphoepithelial lesions, characterized by close interactions among epithelial, T, and B cells. Such lesions may be observed in SS patients undergoing lymphomatous transformation of salivary glands (6). Furthermore, most Il-12rb2-KO mice had serum ANA but not anti-DNA antibodies (5). A striking up-regulation of IL-6 expression was detected in splenocytes as well as in liver and kidney lymphoid infiltrates from H-12rb2-KO versus wild-type mice. Late in life, some of the Il-12rb2-KO mice developed adenocarcinoma or bronchoalveolar lung carcinoma, lymph node plasmacytoma, and amyloidosis.
机译：致编辑：Vosters等人（1）最近报道，易发生自身免疫性白介素12（IL-12）的转基因小鼠代表了干燥综合征（SS）的新模型（1）。通过在甲状腺球蛋白启动子的控制下表达具有生物活性的IL-12 p70异二聚体来产生IL-12转基因动物。小鼠表现出高血清水平的EL-12，以及与人SS相似的甲状腺，肺，唾液和泪腺的IL依赖性淋巴细胞浸润（2）。 Vosters和同事证明，与野生型对照相比，IL-12转基因小鼠的唾液流量减少。唾液腺显示增加的淋巴细胞浸润和减少的痤疮数量，并且始终检测到血清抗SSB / La抗体（SS的血清学标志[3]）以及抗核抗体（ANAs）。IL-12与异二聚体受体结合。 （IL-12R）由j81和j32链组成。 IL-12R / 31还是IL-23（一种与IL-12相关的细胞因子）受体的成分，而IL-12R / 32仅是IL-12R的链。几年前，在关于IL-12R | 82在B细胞淋巴增生性疾病中的作用的研究中（4），我们研究了是否产生C57BL / 6J //-12rb2-敲除（KO）小鼠但不能利用它，自发性发展性淋巴增生性疾病或免疫功能异常（5）。这些小鼠从4个月大时开始表现出亚临床多器官淋巴样浸润，涉及肾脏，肝，肺和唾液腺。这一发现随着年龄的增长而增加，而在野生型小鼠中则完全没有。浸润具有以系统性血管炎为特征的小动脉周围分布，通常组织成异位的淋巴滤泡样结构，形成于外周淋巴结阳性血管附近，包含活化的B细胞的核心与滤泡树突状细胞的混合，并以小的成熟为边界T淋巴细胞（5）。有趣的是，II-12rb2-KO小鼠的腮腺和上颌下腺也可能发展淋巴上皮病变，其特征在于上皮，T和B细胞之间的紧密相互作用。在经历唾液腺淋巴瘤转化的SS患者中可能会观察到此类病变（6）。此外，大多数Il-12rb2-KO小鼠具有血清ANA，但没有抗DNA抗体（5）。与野生型小鼠相比，在H-12rb2-KO的脾细胞以及肝和肾淋巴样浸润中检测到了IL-6表达的显着上调。在生命的晚期，某些Il-12rb2-KO小鼠发展成腺癌或支气管肺泡癌，淋巴结浆细胞瘤和淀粉样变性。

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