The Role of Th2 Immunity in Late-stage silicosis

描述（由申请人提供）：吸入二氧化硅导致慢性炎症和纤维化，肺功能下降，对自身免疫性疾病的易感性增加。矽肺病的发病过程与免疫系统中Th1和Th2两个分支的介质有关，有证据表明，每个分支都起着不同的作用。具体来说，Th1炎症在急性期上调，而Th2细胞因子在晚期与纤维化有关。肺免疫的一个主要组成部分是肺巨噬细胞。巨噬细胞通过在先天免疫系统和适应性免疫系统之间发挥中介作用，具有调节免疫应答的能力。肺泡巨噬细胞（AM）在矽肺中起着至关重要的作用，包括据报道的吞噬二氧化硅摄取。最近，巨噬细胞的一个亚群，选择性激活（aaMac），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，以及在矽肺晚期从Th1炎症转向th2定向纤维化的机制。

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.