结核病和结节病均以肺部肉芽肿增生为主要病理学改变，流行病学发现两种疾病病人的男女性别比相反，而机理尚不清楚。课题前期基于结核肉芽肿标本和临床数据分析发现，男性较女性病人的肉芽肿坏死面积更大；进一步，在年龄配对的不吸烟初治结核患者，男性较女性痰菌量更大，空洞率更高，也反映男性结核病人有更严重的肺损伤，而这种趋势在老年男性显著降低。相反，结节病人则表现女性更年期高发病率的趋势；提示性激素作用下男女性肺组织和外周免疫微环境的差异可能影响了两种疾病的病理发生。项目将通过对健康对照及肺结核和结节病人外周血、肺组织转录组学、蛋白组学、代谢组学等研究，结合流式细胞仪检测、蛋白芯片和免疫组化检测比较，了解男女性肺部应对结核菌感染的不同反应，及结节病人肺部免疫特征，进而结合细胞和动物模型，以期揭示结核病和结节病发病的细胞组织代谢和免疫基础，为基于不同性别人群的结核病预防和精准治疗以及结节病的诊断提供新思路。

Pulmonary tuberculosis (PTB) and sarcoidosis are both granulomatous diseases but with opposite sex bias in incidences. More men than women suffered from tuberculosis while in sarcoidosis vice versa. Our previous work based on analyses of the granuloma biopsies and clinical data indicated that, larger caseous necrotic foci were associated with men. In consistent with this, in no-smoking TB patients without anti-TB treatment history and immune-associated comorbidities, men with PTB had a higher bacterial counts in sputum smear with higher ratios of cavities than age-matched women with PTB, which reflects that infection of Mycobacterium tuberculosis results more severe lung injuries in men than in women. Intriguingly, this higher cavity-forming ratio in men (15-74) drops greatly in elderly (>75 years) men, which become close to the ratio in women.On the contrary, sarcoidosis is mostly reported in women at age of menopause (45-60 years).Our hypose is that sex differences and especially the level of sex hormones may determine the microenvironment in lung and peripheral blood, therefore, results in differential immune responses to Mtb. and inducing factor(s) for sarcoidosis. To clarify this hypothesis, we will combine the omics (transcriptomics, proteomics, metabolomics) methods to investigate and compare the differences between peripheral blood, BAL fluids, and lung tissues from men and women with matched age PTB and sarcoidosis. The results of the study may help to reveal the physiological and immunological basis for sex biases in tuberculosis and sarcoidosis, which may form the basis for prevention and precision therapy of TB and help to the diagnosis of sarcoidosis.