EOH Journal Club

EOH Journal Club Seminar - Fall 2018

Thursday 10/11 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room
EOH Journal Club Seminar - Fall 2018

Date: Thursday October 11th, 2018

Time: 11am - 12pm

Presenter: Shuo Cao

Paper: CCR10+ epithelial cells from idiopathic pulmonary fibrosis lungs drive remodeling.

Habiel DM, Espindola MS, Jones IC, Coelho AL, Stripp B, Hogaboam CM.

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 CCR10hi epithelial cells coexpress EphA3 and ephrin A signaling induces the expression of CCR10 by these cells. Finally, EphA3+CCR10hi epithelial cells induce more consistent lung remodeling in NSG mice relative to EphA3-CCR10lo epithelial cells. Our results suggest that targeting epithelial cells, highly expressing CCR10, may be beneficial in IPF.

Cell Biology; Collagens; Fibrosis; Mouse models; Pulmonology

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Last Updated On Friday, September 21, 2018 by Orbell, Adam W
Created On Friday, September 21, 2018