Sensing of apoptotic cells through Axl causes lung basal cell proliferation in inflammatory diseases
Sensing of apoptotic cells through Axl causes lung basal cell proliferation in inflammatory diseases
复制标题
在炎症性疾病中，通过Axl对凋亡细胞的感知导致肺基底细胞增殖。
DOI：
10.1084/jem.20171978
复制
发表时间：
2019-09-01
影响因子：
15.3
通讯作者：
Hussell, Tracy
中科院分区：
文献类型：
--
作者：
Fujino, Naoya;Brand, Oliver J.;Hussell, Tracy
上皮细胞的增殖、分裂和分化是炎症后屏障修复的关键，但这一过程的初始触发因素尚不清楚。在这里，我们定义了受体酪氨酸激酶Ax1对细胞凋亡的感知是气管基底层细胞扩张、细胞周期重入和细胞对称分裂的关键指标。此外，一旦气管基底细胞池扩大，AXL的沉默就需要它们的分化。AXL的基因缺失触发了不对称的细胞分裂，导致上皮分化和纤毛细胞再生。这一发现对慢性炎症性肺部疾病患者中与上皮屏障功能障碍、基底细胞增生和死亡细胞持续周转相关的情况有一定的意义。
Epithelial cell proliferation, division, and differentiation are critical for barrier repair following inflammation, but the initial trigger for this process is unknown. Here we define that sensing of apoptotic cells by the TAM receptor tyrosine kinase Axl is a critical indicator for tracheal basal cell expansion, cell cycle reentry, and symmetrical cell division. Furthermore, once the pool of tracheal basal cells has expanded, silencing of Axl is required for their differentiation. Genetic depletion of Axl triggers asymmetrical cell division, leading to epithelial differentiation and ciliated cell regeneration. This discovery has implications for conditions associated with epithelial barrier dysfunction, basal cell hyperplasia, and continued turnover of dying cells in patients with chronic inflammatory pulmonary diseases.