IL-14 alpha, the nexus for primary Sjogren's disease in mice and humans
IL-14 alpha, the nexus for primary Sjogren's disease in mice and humans
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DOI：
10.1016/j.clim.2008.10.006
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发表时间：
2009-03-01
影响因子：
8.6
通讯作者：
Ambrus, Julian L.
中科院分区：
文献类型：
--
作者：
Shen, Long;Suresh, Lakshmanan;Ambrus, Julian L.
为探讨白细胞介素14α(IL-14a)在干燥综合征(SS)中的作用，我们采用定量RT-PCR方法检测了干燥综合征(SS)患者和正常对照组外周血淋巴细胞(PBL)中IL-14a的表达。此外，对从出生6周到死亡的转基因IL-14a小鼠进行了组织学和免疫学特征的分析。与年龄、性别和种族匹配的正常对照组相比，患有原发和继发性干燥综合征的患者外周血中IL-14a的表达水平有统计学意义上的高。在IL-14a表达持续增加的转基因小鼠中，先前被证明患有高丙种球蛋白血症、自身抗体、腮腺淋巴细胞浸润、轻度免疫复合体介导的肾脏疾病和大B细胞淋巴瘤。在这篇文章中，我们扩展这些观察以证明这些小鼠发育ALL。临床和免疫学特征：第1期早期高丙种球蛋白血症和自身抗体产生；第2期唾液腺功能下降，早期仅有颌下腺淋巴细胞浸润，但抗体沉积在颌下腺和腮腺；第3期颌下腺、腮腺和泪腺淋巴细胞浸润，伴有B、T淋巴细胞和浆细胞，伴有间质性肺部疾病和轻度肾脏疾病；第4期大B细胞淋巴瘤。因此，IL-14a在干燥病的病理生理学中起重要作用。IL-14a转基因小鼠是一种新的动物模型，可用于了解干燥病的病理生理机制。(C)2008 Elsevier Inc.保留所有权利。
To evaluate the role of interteukin 14 alpha (IL-14a) in Sjogren's syndrome (SS), we evaluated the expression of IL-14a in the peripheral blood lymphocytes (PBL) of patients with primary and secondary SS and normal controls by quantitative RT-PCR. In addition, transgenic IL-14a mice were analyzed from 6 weeks of age to death for both histological and immunological features of Sjogren's disease.Patients with both primary and secondary Sjogren's syndrome expressed IL-14a at statistically higher levels in their peripheral blood compared to normal controls matched for age, sex and ethnic group. Transgenic mice in which IL-14a expression was increased constitutively were previously demonstrated to develop hypergammaglobulinemia, autoantibodies, infiltration of the parotid glands with lymphocytes, mild immune-complex mediated renal disease and large B cell lymphoma. In this paper we expand these observations to demonstrate that these mice develop all. the clinical and immunological features of primary Sjogren's disease in the same relative time frame as patients with primary Sjogren's disease: stage 1-early hypergammaglobulinemia and autoantibody production, stage 2-decreased salivary gland function with early lymphocytic infiltration of the submandibular glands only, but antibody deposition in the submandibular and parotid glands, stage 3-lymphocytic infiltration of the submandibular, parotid and lacrimal glands with B and T lymphocytes and plasma cells along with interstitial lung disease and mild renal disease, and stage 4-large B cell lymphoma. Thus IL-14a is important in the pathophysiology of Sjogren's disease. The IL-14a transgenic mouse is a novel animal model that can be utilized to understand the pathophysiology of Sjogren's disease. (C) 2008 Elsevier Inc. All rights reserved.