Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
CCR10+ epithelial cells from idiopathic pulmonary fibrosis lungs drive remodeling
David M. Habiel, Milena S. Espindola, Isabelle C. Jones, Ana Lucia Coelho, Barry Stripp, Cory M. Hogaboam
David M. Habiel, Milena S. Espindola, Isabelle C. Jones, Ana Lucia Coelho, Barry Stripp, Cory M. Hogaboam
View: Text | PDF
Research Article Cell biology Pulmonology

CCR10+ epithelial cells from idiopathic pulmonary fibrosis lungs drive remodeling

  • Text
  • PDF
Abstract

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.

Authors

David M. Habiel, Milena S. Espindola, Isabelle C. Jones, Ana Lucia Coelho, Barry Stripp, Cory M. Hogaboam

×

Figure 2

CCR10lo-expressing epithelial cells engraft and promote fibrosis in the lungs of humanized NSG mice.

Options: View larger image (or click on image) Download as PowerPoint
CCR10lo-expressing epithelial cells engraft and promote fibrosis in the ...
(A) Magnetically sorted IPF CCR10hi and CCR10lo cells were intravenously administered into NSG mice (0.25 million cells/mouse) and after 35 days, the mice were sacrificed, their lungs were collected for histological, biochemical, and flow cytometric analyses. (B) Shown is an image of IPF CCR10hi-humanized NSG mice, 31 days after cellular administration. (C) Shown are representative images of lung tissues, from naive (left), IPF CCR10hi-humanized (middle), and IPF CCR10lo-humanized (right) NSG groups taken at ×100 magnification. (D) Depicted is the hydroxyproline concentration in the lungs of naive, nonhumanized, or humanized NSG mice that received IPF CCR10hi or CCR10lo cells. n = 5–10 mice/group. Data shown are the mean ± SEM. ns, not significant; *P ≤ 0.05 via 1-way ANOVA corrected for multiple comparison via Dunnett’s test. (E) CCR10hi or CCR10lo humanized NSG mouse lung suspensions were analyzed by flow cytometry for human CD45, EpCAM, and/or CCR10 expression. Depicted are representative dot plots showing EpCAM+ cells (left) and the percentage of EpCAM+ cells expressing cell surface CCR10 (right) in IPF CCR10hi (top) and CCR10lo (bottom) humanized NSG lungs. (F) Shown is the average number of EpCAM+CCR10+ cells in IPF CCR10hi and CCR10lo humanized NSG mice. n = 5/group. Data shown are the mean ± SEM. *P ≤ 0.05 via 2-tailed Mann-Whitney nonparametric test. (G) IPF lung explant cells were stained with anti-CD45, anti-EpCAM, and anti-CCR10 antibodies. Shown is the mean GMFI for CCR10 staining on CD45+ and CD45–EpCAM+ cells. n = 12/group. Data shown are the mean ± SEM. ****P ≤ 0.0001 via 2-tailed Mann-Whitney nonparametric test. IPF, idiopathic pulmonary fibrosis; NSG, NOD Cg-PrkdcSCID IL2rgTm1wilSzi.

Copyright © 2026 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts