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首页> 外文期刊>The journal of clinical investigation >Thymus-specific serine protease controls autoreactive CD4 T cell development and autoimmune diabetes in mice
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Thymus-specific serine protease controls autoreactive CD4 T cell development and autoimmune diabetes in mice

机译：胸腺特异性丝氨酸蛋白酶控制小鼠自身反应性CD4 T细胞发育和自身免疫性糖尿病

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Type 1 diabetes is a chronic autoimmune disease in which genetic predispositions affect the immune system, leading to a loss of T cell tolerance to β cells and consequent T cell–mediated destruction of insulin-producing islet cells. Genetic studies have suggested that PRSS16 is linked to a diabetes susceptibility locus of the extended HLA class I region in humans. PRSS16 encodes what we believe to be a novel protease, thymus-specific serine protease (TSSP), which shows predominant expression in thymic epithelial cells and is suspected to have a restricted role in the class II presentation pathway. Consistently, Tssp is necessary for the intrathymic selection of few class II–restricted T cell receptor specificities in B6 mice. To directly assess the role of Tssp in autoimmune diabetes, we generated Tssp-deficient (Tssp°) NOD mice. While remaining immunocompetent, Tssp° NOD mice were protected from diabetes and severe insulitis. Diabetes resistance of Tssp° NOD mice was a property of the CD4 T cell compartment that is acquired during thymic selection and correlated with an impaired selection of CD4 T cells specific for islet antigens. Hence, in the NOD mouse, Tssp is a critical regulator of diabetes development through the selection of the autoreactive CD4 T cell repertoire.
机译：1型糖尿病是一种慢性自身免疫性疾病，其遗传易感性影响免疫系统，导致T细胞对β细胞的耐受性丧失，进而导致T细胞介导的产生胰岛素的胰岛细胞破坏。遗传研究表明PRSS16与人类HLA I类区域扩展的糖尿病易感性基因位点相关。 PRSS16编码我们认为是一种新型的蛋白酶，胸腺特异性丝氨酸蛋白酶（TSSP），在胸腺上皮细胞中主要表达，并怀疑在II类呈递途径中作用有限。一致地，Tssp对于在B6小鼠中少数II类限制性T细胞受体特异性的胸腺内选择是必需的。为了直接评估Tssp在自身免疫性糖尿病中的作用，我们生成了Tssp缺陷（Tssp°）NOD小鼠。在保持免疫能力的同时，Tssp°NOD小鼠免受糖尿病和严重的岛炎的影响。 Tssp°NOD小鼠的糖尿病抵抗力是在胸腺选择过程中获得的CD4 T细胞区室的特性，与胰岛抗原特异的CD4 T细胞选择受损有关。因此，在NOD小鼠中，通过选择自身反应性CD4 T细胞库，Tssp是糖尿病发展的关键调节剂。

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