上皮细胞可塑性和固有免疫激活促进呼吸道病毒感染后肺组织重塑。

Epithelial plasticity and innate immune activation promote lung tissue remodeling following respiratory viral infection.

机构信息

Department of Medicine, Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.

出版信息

Nat Commun. 2023 Sep 19;14(1):5814. doi: 10.1038/s41467-023-41387-3.

Epithelial plasticity has been suggested in lungs of mice following genetic depletion of stem cells but is of unknown physiological relevance. Viral infection and chronic lung disease share similar pathological features of stem cell loss in alveoli, basal cell (BC) hyperplasia in small airways, and innate immune activation, that contribute to epithelial remodeling and loss of lung function. We show that a subset of distal airway secretory cells, intralobar serous (IS) cells, are activated to assume BC fates following influenza virus infection. Injury-induced hyperplastic BC (hBC) differ from pre-existing BC by high expression of IL-22Ra1 and undergo IL-22-dependent expansion for colonization of injured alveoli. Resolution of virus-elicited inflammation results in BC to IS re-differentiation in repopulated alveoli, and increased local expression of protective antimicrobial factors, but fails to restore normal alveolar epithelium responsible for gas exchange.

上皮可塑性已在遗传耗尽干细胞的小鼠肺部中被提出，但生理相关性尚不清楚。病毒感染和慢性肺病在肺泡中干细胞丧失、小气道基底细胞（BC）增生和固有免疫激活方面具有相似的病理特征，这些特征导致上皮重塑和肺功能丧失。我们表明，流感病毒感染后，一部分远端气道分泌细胞，即小叶内浆液细胞（IS），被激活以获得 BC 命运。损伤诱导的增生性 BC（hBC）与预先存在的 BC 不同，其高表达 IL-22Ra1，并经历 IL-22 依赖性扩张以殖民受损的肺泡。病毒引发的炎症的消退导致再填充肺泡中 BC 向 IS 的再分化，以及局部保护性抗菌因子表达增加，但未能恢复负责气体交换的正常肺泡上皮。