Domain-specific role of IL-17RA in controlling Klebsiella pneumoniae lung infection

摘要 IL-17是肺炎克雷伯氏菌（Klebsiella pneumoniae，KP）免疫的重要介质。缺乏IL-17信号传导的动物模型 或具有IL-17受体（IL-17 R）缺乏的患者易患KP肺炎。虽然大量的研究 目前的研究主要集中在Th 17细胞是如何产生和调节的，IL-17及其受体的作用机制等方面。 受体IL-17 R介导相关疾病过程中的特异性下游信号，如KP肺炎， 没有完全阐明。我们在小鼠模型中了解KP肺炎的努力表明， IL-17 RA，也称为CBAD，对于控制这种感染是必不可少的。因此，我们建议确定 IL-17 RA CBAD结构域限制KP肺炎的免疫和分子机制。我们将 还进行平行分析以通过单细胞RNASeq评估细胞类型特异性应答。这些发现 从这个建议中产生的将有助于我们理解IL-17依赖的信号传导机制， 肺炎可以得到控制，并以单细胞分辨率评估肺免疫应答。

ABSTRACT IL-17 is an essential mediator of immunity to Klebsiella pneumoniae (KP). Animal models lacking IL-17 signaling or having IL-17 receptor (IL-17R) deficiency are susceptible to KP pneumonia. Although considerable research effort has focused on how Th17 cells are generated and regulated, the mechanisms by which IL-17 and its receptor IL-17R mediate specific downstream signals in relevant disease processes such as KP pneumonia are not fully elucidated. Our efforts to understand KP pneumonia in mouse models revealed that the distal domain of IL-17RA, also known as CBAD, is indispensable to control this infection. Thus, we propose to determine the immune and molecular mechanisms by which the IL-17RA CBAD domain constrains KP pneumonia. We will also perform parallel analyses to evaluate the cell-type-specific response by single-cell RNASeq. The findings generated from this proposal will help us understand IL-17- dependent signaling mechanism by which KP pneumonia can be controlled and to evaluate the lung immune response at a single cell resolution.