肺结节病的免疫分子机制及干预研究

Sarcoidosis is a multisystem granulomatous inflammatory disorder that most commonly affects the lungs and intrathoracic lymph nodes. The etiology is unclear and clinical manifestations are protean. In China, it is extremely difficult to make a differential diagnosis between sarcoidosis and sputum negative Mycobacterium tuberculosis. Prognosis may be very different, some patients resolve themselves without treatment, some patients tending to recrudesce during glucocorticoid therapy, while some patients even developing pulmonary fibrosis. Plenty of studied point that immunity imbalance of CD4+ T-lymphocyte subsets and activation or proliferation of monocyte-macrophages play key roles in the pathogenesis of sarcoidosis. What kind of characteristic changes happened to the respiratory tract and the whole body immunity function? What kinds of immune cells or cytokines are involved? How strongly related is it to the final outcome of sarcoidosis? Is there any immune molecular marker in different prognosis patients? What is the mechanism of the formation of sarcoidosis? In the previous study we found that infection and inhaled dust can induce sarcoidosis. We also found that Th17/Treg cells may play the role in the progresses of sarcoidosis. In current study, we will utilize advanced technological methods including molecular, cell, animal model and patients' clinical data to analyze the characteristic changes of the innate and adaptive immunity function in the respiratory tract and the whole body, reveal the etiology and immunological molecular mechanism of sarcoidosis, and demonstrate the mechanism of self-resolving, relapse and worsening into pulmonary fibrosis in the process of sarcoidosis. This study will provide new insights for diagnosis and treatment of sarcoidosis patients.

结节病是一种累及全身多器官的系统性肉芽肿性疾病，90%以上累及肺部。病因和发病机制不明，临床表现多样，与痰菌阴性结核病鉴别困难。临床转归差异很大，部分可自愈或对激素反应良好，部分治疗后复发或进展为肺纤维化。结节病形成与免疫功能紊乱有关，尤其是CD4+T淋巴细胞亚群失衡、单核-巨噬细胞的异常激活与增殖。但确切的机制尚不清楚。结节病患者全身和肺组织局部免疫功能的特征性变化如何？涉及哪些关键免疫细胞及分子？不同预后与免疫功能变化的关联性？结节病肉芽肿病因为何？都是急待解决的关键科学问题。我们的研究提示感染和粉尘吸入可能是结节病的致病原，Th17/Treg免疫细胞的功能变化在结节病发生发展中起了重要作用。本研究拟从分子、细胞、动物模型及临床动态资料等多角度研究结节病全身及肺局部免疫应答的特征性变化，探索结节病病因，确定结节病不同转归的免疫分子标记物，为结节病的诊治和预后判断提供新方法和新思路。

结节病是一种累及全身多器官的系统性肉芽肿性疾病，90%以上累及肺部。病因和发病机制不明，临床表现多样，与痰菌阴性结核病鉴别困难。临床转归差异很大，部分可自愈或对激素反应良好，部分治疗后复发或进展为肺纤维化。结节病形成与免疫功能紊乱有关，尤其是CD4+T淋巴细胞亚群失衡、单核-巨噬细胞的异常激活与增殖。但确切的机制尚不清楚。结节病患者全身和肺组织局部免疫功能的特征性变化如何？涉及哪些关键免疫细胞及分子？不同预后与免疫功能变化的关联性？结节病肉芽肿病因为何？都是急待解决的关键科学问题。我们的研究提示感染和粉尘吸入可能是结节病的致病原，Th17/Treg免疫细胞的功能变化在结节病发生发展中起了重要作用。本研究从分子、细胞、动物模型及临床动态资料等多角度研究结节病全身及肺局部免疫应答的特征性变化，探索结节病病因，确定结节病不同转归的免疫分子标记物。以通讯作者发表标注项目资助号的SCI论文13篇，注册相关临床研究2项，培养研究生10余人，本项目成果有望寻找到结节病特征性生物标记及治疗干预靶点，将科学研究成果转化为临床应用，尤其重要的是在结节病与菌阴结核病的鉴别诊断新方法方面将有所建树，为结节病与大量结核病的鉴别诊断提供新的手段。