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

摘要 IL-17是肺炎克雷伯菌免疫的重要介质。缺乏IL-17信号的动物模型 或IL-17受体(IL-17R)缺乏易患肺炎。尽管有大量的研究 这方面的努力主要集中在Th17细胞是如何产生和调节的，IL-17和IL-17的作用机制 受体IL-17R在肺炎等相关疾病过程中介导特定的下游信号 没有完全阐明的。我们在小鼠模型中理解KP肺炎的努力揭示了远端结构域 IL-17RA，也被称为CBAD，对于控制这种感染是不可或缺的。因此，我们建议确定 IL-17RA CBAD结构域抑制KP肺炎的免疫和分子机制。我们会 还可以执行平行分析，以评估单细胞RNAseq对细胞类型的特定反应。调查结果 这一提议将有助于我们理解依赖IL-17的信号转导机制， 肺炎是可以控制的，并能在单个细胞分辨率上评估肺免疫反应。

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.