CCR10+ epithelial cells from idiopathic pulmonary fibrosis lungs drive remodeling.
JCI INSIGHT(2018)
摘要
Idiopathic pulmonary fibrosis (IPF) is a devastating fibrotic lung disease of unknown etiology and limited therapeutic options. In this report, we characterize what we believe is a novel CCR10(+) epithelial cell population in IPF lungs. There was a significant increase in the percentage of CCR10(+) epithelial cells in IPF relative to normal lung explants and their numbers significantly correlated to lung remodeling in humanized NSG mice. Cultured CCR10-enriched IPF epithelial cells promoted IPF lung fibroblast invasion and collagen 1 secretion. Single-cell RNA sequencing analysis showed distinct CCR10(+) epithelial cell populations enriched for inflammatory and profibrotic transcripts. Consistently, cultured IPF but not normal epithelial cells induced lung remodeling in humanized NSG mice, where the number of CCR10(+) IPF, but not normal, epithelial cells correlated with hydroxyproline concentration in the remodeled NSG lungs. A subset of IPF CCR10(hi) epithelial cells coexpress EphA3 and ephrin A signaling induces the expression of CCR10 by these cells. Finally, EphA3(+)CCR10(hi) epithelial cells induce more consistent lung remodeling in NSG mice relative to EphA3(-)CCR10(lo) epithelial cells. Our results suggest that targeting epithelial cells, highly expressing CCR10, may be beneficial in IPF.
更多查看译文
关键词
Cell Biology,Collagens,Fibrosis,Mouse models,Pulmonology
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要