Inflammatory and immune dysregulation associated lung disease

免疫或炎症调节障碍累及肺部的范围可以从原发性表现（如结节病）或相对轻微的表现（如对分枝杆菌病的孟德尔易感性免疫缺陷）。虽然这两者都可能与肺部肉芽肿性炎症有关，但临床肺部表现和治疗策略却截然不同。慢性呼吸道感染实验室（LCAI）寻求利用与临床免疫学和微生物学实验室以及NIAID和NIAMS内专注于这些疾病的其他分支机构的密切合作，描述已知和新出现的免疫和炎症性疾病的肺部表现。在过去的一年里，我们继续与北卡罗来纳大学的研究人员合作，以更好地定义STAT3在改变气道清除中的作用。作为合作的一部分收集的气道细胞被UNC合作者用来表征气道上皮与新型SARS CoV-2病毒的相互作用，为其从上呼吸道到下呼吸道的转移提供了一个合理的解释。骨髓来源的间充质基质细胞在体外被证明可以调节与结节病相关的巨噬细胞相关的炎症，为这种疾病的潜在治疗干预奠定了基础。肺功能以2例罕见病例为特征：多发性内分泌瘤2B和先天性角化不良。最后，一种新的免疫调节紊乱，PI3Kgamma缺乏症在一名复发性淋巴细胞为主的肺部浸润患者中被描述，并从一种新的小鼠模型中获得了对炎症途径的见解。

The pulmonary involvement in disorders of immune or inflammatory regulation can range from a primary manifestation such as with sarcoidosis or a relatively minor manifestations such as seen with the Mendelian Susceptibility to Mycobacterial Disease immune deficiencies. While both of these can be associated with granulomatous inflammation in the lung, the clinical pulmonary manifestations are quite different as are the management strategies. The Laboratory of Chronic Airway Infection (LCAI) has sought to capitalize on the close collaboration with the Laboratory of Clinical Immunology and Microbiology and other branches within the NIAID and NIAMS focused on these disorders to describe the pulmonary manifestations of known and emerging immune and inflammatory diseases. Over the past year we have continued collaboration with investigators at the University of North Carolina to better define the role of STAT3 in altered airway clearance. Airway cells collected as part of this collaboration were utilized by UNC collaborators to characterize the airway epithelial interaction with the novel SARS CoV-2 virus to provide a plausible explanation for its transit from the upper to lower respiratory tract. Bone marrow derived mesenchymal stromal cells were shown to modulate in vitro the inflammation associated with sarcoidosis associated macrophage, setting the stage for a potential therapeutic intervention in this disease. Pulmonary function was characterised in 2 rare conditions, Multiple Endocrine Neoplasia 2B and dyskeratosis congenita. Finally, a new disorder of immune regulation, PI3Kgamma deficiency was described in a patient with recurring lymphocyte-predominant lung infiltrates and insights into the inflammatory pathway were gleaned from a novel mouse model.