Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Antibody-mediated depletion of CCR10+EphA3+ cells ameliorates fibrosis in IPF
Miriam S. Hohmann, … , Lynne A. Murray, Cory M. Hogaboam
Miriam S. Hohmann, … , Lynne A. Murray, Cory M. Hogaboam
Published May 4, 2021
Citation Information: JCI Insight. 2021;6(11):e141061. https://doi.org/10.1172/jci.insight.141061.
View: Text | PDF
Research Article Pulmonology

Antibody-mediated depletion of CCR10+EphA3+ cells ameliorates fibrosis in IPF

  • Text
  • PDF
Abstract

Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant repair that diminishes lung function via mechanisms that remain poorly understood. CC chemokine receptor (CCR10) and its ligand CCL28 were both elevated in IPF compared with normal donors. CCR10 was highly expressed by various cells from IPF lungs, most notably stage-specific embryonic antigen-4–positive mesenchymal progenitor cells (MPCs). In vitro, CCL28 promoted the proliferation of CCR10+ MPCs while CRISPR/Cas9–mediated targeting of CCR10 resulted in the death of MPCs. Following the intravenous injection of various cells from IPF lungs into immunodeficient (NOD/SCID-γ, NSG) mice, human CCR10+ cells initiated and maintained fibrosis in NSG mice. Eph receptor A3 (EphA3) was among the highest expressed receptor tyrosine kinases detected on IPF CCR10+ cells. Ifabotuzumab-targeted killing of EphA3+ cells significantly reduced the numbers of CCR10+ cells and ameliorated pulmonary fibrosis in humanized NSG mice. Thus, human CCR10+ cells promote pulmonary fibrosis, and EphA3 mAb–directed elimination of these cells inhibits lung fibrosis.

Authors

Miriam S. Hohmann, David M. Habiel, Milena S. Espindola, Guanling Huang, Isabelle Jones, Rohan Narayanan, Ana Lucia Coelho, Justin M. Oldham, Imre Noth, Shwu-Fan Ma, Adrianne Kurkciyan, Jonathan L. McQualter, Gianni Carraro, Barry Stripp, Peter Chen, Dianhua Jiang, Paul W. Noble, William Parks, John Woronicz, Geoffrey Yarranton, Lynne A. Murray, Cory M. Hogaboam

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

Supplemental data - Download (25.92 MB)

Advertisement

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts