CD4_T-cell_Immunity_in_the_Lung

肺中的 CD4_T 细胞免疫

• 批准号: 10321572
• 负责人: JAY K KOLLS
• 金额: $ 86.92万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10321572
• 关键词: Adult; Area; Bacterial Pneumonia; CD209 gene; CD4 Positive T Lymphocytes; Cells; Child; Granulocyte-Macrophage Colony-Stimulating Factor; Host Defense; Host resistance; Immunity; Interleukin-17; Laboratories; Light; Lung; Memory; Morbidity - disease rate; Pathway interactions; Pneumocystis; Pneumonia; Protein Isoforms; Research; Role; STAT3 gene; Seminal; Testing; Tissues; cytokine; insight; interleukin-21 receptor; interleukin-22; mortality; novel; novel therapeutics; novel vaccines; pathogen; pneumonia treatment; prevent

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.

抽象的 肺炎仍然是世界上儿童的第一杀手，也是发病率和死亡率的主要原因 我们的实验室已确定美国儿童死亡率和成人死亡率的第八位。 关于宿主防御细胞外病原体的机制的开创性见解 – 特别是在 17 型细胞因子——IL-17 和 IL-22 领域，我们已经发现了新型细胞因子。 调节宿主对肺孢子虫免疫的途径，包括 CD4+ T 细胞内在 IL21R 表达和 STAT3 激活我们将确定 CD4+ T 细胞 STAT3 如何调节。 宿主抵抗并测试 IL-22、GM-CSF 和 CD209 亚型的具体作用。 我们将研究 IL-22RA2 在调节肺中游离 IL-22 的可用性方面的作用， 研究组织驻留记忆细胞在宿主防御细菌中的贡献 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。