CD4_T-cell_Immunity_in_the_Lung

摘要 肺炎仍然是世界上儿童的头号杀手，是发病和死亡的主要原因。 美国儿童死亡率和成人死亡率的第8大原因。我们的实验室 对宿主防御细胞外病原体的潜在机制的开创性见解- 特别是在17型细胞因子-IL-17和IL-22领域。我们发现了一种新的 调节宿主抗肺孢子虫免疫的途径，包括CD 4 + T细胞固有 IL 21 R表达和STAT 3活化。我们将确定CD 4 + T细胞STAT 3如何调节 宿主抗性和测试IL-22、GM-CSF和CD 209同种型的特异性作用。此外 我们将研究IL-22 RA 2在调节肺中游离IL-22的可用性中的作用， 研究组织驻留记忆细胞在宿主防御细菌中的作用 肺炎在此R35下进行的研究将为肺部宿主提供新的线索 可用于减少全球肺炎死亡率负担的防御措施， 发病率。

Abstract Pneumonia remains the #1 killer of children in the world and is a leading cause of morbidity and mortality in children in the US and the #8 cause of mortality in adults. Our laboratory has made seminal insights in mechanisms underlying host defense against extracelluar pathogens – particularly in the area of type 17 cytokines –IL-17 and IL-22. We have identified novel pathways that regulate host immunity against Pneumocystis including CD4+ T-cell intrinsic IL21R expression and STAT3 activation. We will determine how CD4+ T-cell STAT3 regulates host resistance and test the specific roles of IL-22, GM-CSF and CD209 isoforms. Furthermore we will examine the role of IL-22RA2 in regulating the availability of free IL-22 in the lung and study the contributions of tissue resident memory cells in host defense against bacterial pneumonia. The research prosed under this R35 will shed new light on pulmonary host defenses that can be exploited to reduce the global burden of pneumonia mortality and morbidity.