Autoimmunity against a tissue kallikrein in IQI/Jic mice - A model for Sjogren's syndrome
Autoimmunity against a tissue kallikrein in IQI/Jic mice - A model for Sjogren's syndrome
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DOI：
10.1074/jbc.m410157200
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发表时间：
2005-02-04
影响因子：
4.8
通讯作者：
Inaba, A
中科院分区：
文献类型：
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作者：
Takada, K;Takiguchi, M;Inaba, A
我们最近的特点是IQI/Jic小鼠作为干燥综合征（SS），一种慢性自身免疫性疾病在人类的模型。在SS中，局部淋巴细胞浸润到唾液腺和泪腺经常发展到全身外分泌和非外分泌器官的参与，这种疾病的进展机制仍然不清楚。在此，我们报告了IQI/Jic小鼠中各种靶器官共有的自身抗原的鉴定。基于来自患有自身免疫性疾病（> 12周龄）的IQI/ Jic小鼠的血清中的自身抗体的免疫识别鉴定的多肽是组织激肽释放酶（Klk）-1和-13，并且与自身抗体交叉反应。有趣的是，Klk-13，而不是Klk-1，从4周龄起引起IQI/Jic小鼠脾T细胞的增殖反应。此外，在小鼠的唾液腺中观察到Klk-13的表达显著增强，与炎性病变的发展一致。这些结果表明，Klk-13作为自身抗原发挥作用，并可能增加T细胞对通常表达Klk-13的器官的反应，在IQI/Jic小鼠疾病进展的病因学中发挥关键作用。我们的研究结果提供了深入了解SS从器官特异性疾病到系统性疾病的进展中多个器官共享的自身抗原的贡献。
We have recently characterized IQI/Jic mice as a model for Sjogren's syndrome (SS), a chronic autoimmune disease in humans. In SS, local lymphocytic infiltrations into salivary and lacrimal glands frequently develop to the involvement of systemic exocrine and nonexocrine organs, and the mechanism for progression of this disease remains obscure. Herein, we report identification of an autoantigen shared by various target organs in IQI/Jic mice. Polypeptides identified based on immunorecognition by autoantibodies in sera from IQI/ Jic mice affected with autoimmune disease (> 12 weeks of age) were tissue kallikrein (Klk)-1 and -13 and were cross-reactive to the autoantibodies. Interestingly, Klk-13, but not Klk-1, caused a proliferative response of splenic T cells from IQI/Jic mice from the age of 4 weeks onward. In addition, remarkably enhanced expression of Klk-13 was observed in the salivary glands of the mice in accordance with the development of inflammatory lesions. These results indicate that Klk-13 acts as an autoantigen and may increase T cells responsive to organs commonly expressing Klk-13, playing a pivotal role in the etiology of progression of disease in IQI/Jic mice. Our findings provide insights into the contributions of autoantigens shared by multiple organs in the progress of SS from an organ-specific to a systemic disorder.