The Role of Th2 Immunity in Late-stage silicosis

描述(申请人提供)：吸入二氧化硅会导致慢性炎症和纤维化，肺功能下降，增加自身免疫性疾病的易感性。矽肺涉及的疾病过程与Th1和Th2免疫臂的介质有关，证据表明每种介质都发挥着不同的作用。具体来说，Th1炎症在急性期上调，而Th2细胞因子在后期与纤维化有关。肺免疫的一个主要组成部分是肺巨噬细胞。巨噬细胞通过在天然免疫系统和获得性免疫系统之间发挥中介作用来调节免疫反应。肺泡巨噬细胞(AM)在矽肺中起重要作用，据报道包括吞噬细胞摄取二氧化硅。最近，巨噬细胞的一个亚群被交替激活(AaMac)，这与Th2主导的免疫有关。这项建议将确定在接触二氧化硅后aaMac的作用，以及在矽肺后期从Th1炎症向Th2导向的纤维化转换所涉及的机制。

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.