Intermediary Role of Lung Alveolar Type 1 Cells in Epithelial Repair upon Sendai Virus Infection.
Intermediary Role of Lung Alveolar Type 1 Cells in Epithelial Repair upon Sendai Virus Infection.
复制标题
肺泡 1 型细胞在仙台病毒感染后上皮修复中的中介作用。
DOI：
10.1165/rcmb.2021-0421oc
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发表时间：
2022
影响因子：
6.4
通讯作者：
Chen,Jichao
中科院分区：
文献类型：
--
作者：
Hernandez,BelindaJ;Cain,MargoP;Lynch,AnneM;Flores,JoseR;Tuvim,MichaelJ;Dickey,BurtonF;Chen,Jichao
肺上皮形成了对抗呼吸道病原体和有毒化学物质的第一道屏障;然而，人们对90%以上由AT 1（肺泡1型）细胞组成的屏障如何对损伤做出反应知之甚少。使用仙台病毒模型自然感染小鼠，我们发现的证据表明，AT 1细胞有一个中介作用，坚持在该地区耗尽的AT 2细胞，上调IFN反应基因，并从入侵的气道细胞消退。仙台病毒感染动员气道细胞形成肺泡SOX 2+（Sry-box 2+）簇，而不分化成AT 1或AT 2细胞。大的AT 2细胞耗尽区域仍然被AT 1细胞覆盖，我们将其命名为“无AT 2区域”，并被基底和管腔分布的SOX 2+簇所取代。AT 2细胞的增殖和分化主要局限于拓扑学上的远端区域并形成新生肺泡表面，对无AT 2区域的原位修复贡献有限。时间进程单细胞RNA测序分析和RNAscope验证表明增强的免疫反应和改变的生长信号在AT 1细胞。我们全面的时空和全基因组研究强调了迄今为止AT 1细胞在肺损伤修复中未被重视的作用。
The lung epithelium forms the first barrier against respiratory pathogens and noxious chemicals; however, little is known about how more than 90% of this barrier, made of AT1 (alveolar type 1) cells, responds to injury. Using the Sendai virus to model natural infection in mice, we find evidence that AT1 cells have an intermediary role by persisting in areas depleted of AT2 cells, upregulating IFN responsive genes, and receding from invading airway cells. Sendai virus infection mobilizes airway cells to form alveolar SOX2+(Sry-box 2+) clusters without differentiating into AT1 or AT2 cells. Large AT2 cell-depleted areas remain covered by AT1 cells, which we name “AT2-less regions”, and are replaced by SOX2+clusters spreading both basally and luminally. AT2 cell proliferation and differentiation are largely confined to topologically distal regions and formde novoalveolar surface, with limited contribution toin siturepairs of AT2-less regions. Time-course single-cell RNA sequencing profiling and RNAscope validation suggest enhanced immune responses and altered growth signals in AT1 cells. Our comprehensive spatiotemporal and genomewide study highlights the hitherto unappreciated role of AT1 cells in lung injury–repair.