The Role of Th2 Immunity in Late-stage silicosis

Th2 免疫在晚期矽肺中的作用

• 批准号: 7120520
• 负责人: CHRISTOPHER Todd MIGLIACCIO
• 金额: $ 5.59万
• 依托单位: UNIVERSITY OF MONTANA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2007-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7120520
• 关键词: alveolar macrophages; helper T lymphocyte; immunocytochemistry; immunoregulation; interleukin 4; laboratory mouse; pneumoconiosis; polymerase chain reaction; postdoctoral investigator; pulmonary fibrosis /granuloma; silicates; toll like receptor; transforming growth factors

DESCRIPTION (provided by applicant): Inhalation of silica results in chronic inflammation and fibrosis with a decrease in lung function and an increase in susceptibility to autoimmune diseases. The disease process involved in silicosis has been linked with mediators from both the Th1 and Th2 arms of immunity, and evidence suggests each plays a distinct role. Specifically, Th1 inflammation is upregulated in the acute phase, while Th2 cytokines have been associated with fibrosis in the later stages. A major component of lung immunology is the pulmonary macrophage. Macrophages have the ability to regulate immune responses by playing the role of intermediary between the innate and adaptive immune systems. Alveolar macrophages (AM) have been implicated as a vital role in silicosis, including reportedly phagocytic uptake of silica. Recently, a subset of macrophages, alternatively activated (aaMac), has been associated with Th2-dominated immunity. This proposal will determine the role of aaMac following silica exposure, and the mechanism involved in the switch from Th1 inflammation to Th2-directed fibrosis in the later stages of silicosis.

描述（由申请人提供）：吸入二氧化硅会导致慢性炎症和纤维化，并导致肺功能下降和对自身免疫性疾病的易感性增加。硅肺病的疾病过程与 Th1 和 Th2 免疫介质有关，有证据表明每种介质都发挥着不同的作用。具体而言，Th1 炎症在急性期上调，而 Th2 细胞因子在后期与纤维化相关。肺免疫学的一个主要组成部分是肺巨噬细胞。巨噬细胞具有通过发挥先天性免疫系统和适应性免疫系统之间的中介作用来调节免疫反应的能力。肺泡巨噬细胞 (AM) 在硅肺病中发挥着重要作用，据报道包括吞噬细胞对二氧化硅的摄取。最近，巨噬细胞的一个子集（aaMac）被交替激活，与 Th2 主导的免疫有关。该提案将确定 aaMac 在二氧化硅暴露后的作用，以及硅肺后期从 Th1 炎症向 Th2 定向纤维化转变的机制。