Proteolytic generation of the soluble interleukin-6 receptor in vivo (A14*)

该项目涉及循环中的可溶性IL-6R。这种蛋白是由不依赖ADAM17的蛋白水解产生的，因为没有检测到ADAM17活性的人和小鼠表现出正常的可溶性IL-6R水平。可溶性IL-6R水平是炎症性疾病易感性的关键决定因素。该项目将确定负责产生稳态可溶性IL-6R血清水平的蛋白水解活性。我们将筛选候选蛋白酶，并通过相应的敲除小鼠模型验证它们在sIL-6R生成中的作用。

The project deals with the soluble IL-6R in the circulation. This protein is generated by ADAM17-independent proteolysis since humans and mice without detectable ADAM17 activity exhibit normal soluble IL-6R levels. The level of soluble IL-6R is a critical determinant of susceptibility to inflammatory diseases. The project will identify the proteolytic activity responsible for the generation of the steady-state soluble IL-6R serum levels. We will screen candidate proteases and validate their involvement in sIL-6R generation with corresponding knock-out mouse models.