结节病是仅次于特发性肺纤维化的一种临床常见的间质性肺疾病，是以巨噬细胞和Th1淋巴细胞聚集形成非坏死性肉芽肿为病理特点，以肺脏受累为主的疾病，多具有自限性，但约30%结节病患者发展为不可逆性肺纤维化。导致肉芽肿持续和进展为肺纤维化的机制不明。最近研究提示IL-17A可能与肉芽肿和肺纤维化形成有关。本项目基于"IL-17A可诱导结节病进展为肺纤维化"的假设，将通过前瞻性病队列研究评估不同时期结节病肺组织IL-17A的表达水平与疾病分期及预后的关联；通过观察IL-17A刺激结节病患者肺泡巨噬细胞和人成纤维细胞的效应，说明 IL-17A-肺泡巨噬细胞-成纤维细胞网络的促纤维化机制；通过P.acne诱导建立IL-17A基因敲除型和野生型小鼠的结节病模型，并延长对野生型小鼠肺结节病模型的刺激，同时给予IL-17A抗体进行拮抗，证实 IL-17A在结节病肉芽肿形成与转归或肺纤维化形成中的关键作用。

Sarcoidosis is a commonly seen interstital lung disease happened second only to idiopathic pulmonary fibrosis. It is chatacterized by non-ceasating granulomatous collections of macrophages and Th1 lymphocyte. Sarcoidosis commonly involves the lungs ,most cases can resovle spontaneously ,but about 30% sarcoidosis patients progress into irreversible pulmonary fibrosis.The mechanisms of progressive granulomatous and progression towards the fibrotic phase has not been determined. Recent research indicate that IL-17A maybe related to the progressive of granulomatous and pulmonary fibrosis.This project based on the hypothesis"IL-17A plays a central role in sarcoidosis advanced into pulmonary fibrosis",by observing IL-17A levels in lung tissues in different phases and evaluating the relationships between IL-17A levels and disease staging and prognosis by prospective cohort study.By observing the effect which IL-17A stimulates alveolar macrophages from sarcoidosis patients and human fibroblast,to identiy the profibrotic mechanism of IL-17A -Alveolar Machrophages-Fibroblast network.We will use P.acne induced sarcoidosis model in IL-17A-deficient and wild-type murine , prolonging the antigen stimulation and inhibit IL-17A in wild-type sarcoidosis mouse model, to explore the role of IL-17A in granulomatous formation and prognosis or pulmonary fibrosis formation in sarcoidosis.