Your browser doesn't support javascript.
loading
Antibody-mediated depletion of CCR10+EphA3+ cells ameliorates fibrosis in IPF.
Hohmann, Miriam S; Habiel, David M; Espindola, Milena S; Huang, Guanling; Jones, Isabelle; Narayanan, Rohan; Coelho, Ana Lucia; Oldham, Justin M; Noth, Imre; Ma, Shwu-Fan; Kurkciyan, Adrianne; McQualter, Jonathan L; Carraro, Gianni; Stripp, Barry; Chen, Peter; Jiang, Dianhua; Noble, Paul W; Parks, William; Woronicz, John; Yarranton, Geoffrey; Murray, Lynne A; Hogaboam, Cory M.
Affiliation
  • Hohmann MS; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Habiel DM; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Espindola MS; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Huang G; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Jones I; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Narayanan R; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Coelho AL; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Oldham JM; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of California, Davis, Sacramento, California, USA.
  • Noth I; Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
  • Ma SF; Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
  • Kurkciyan A; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • McQualter JL; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Carraro G; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Stripp B; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Chen P; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Jiang D; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Noble PW; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Parks W; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Woronicz J; KaloBios Pharmaceuticals, Inc. (now Humanigen, Inc.), Burlingame, California, USA.
  • Yarranton G; KaloBios Pharmaceuticals, Inc. (now Humanigen, Inc.), Burlingame, California, USA.
  • Murray LA; MiroBio Ltd, Oxford, United Kingdom.
  • Hogaboam CM; Women's Guild Lung Institute, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
JCI Insight ; 6(11)2021 06 08.
Article in En | MEDLINE | ID: mdl-33945505
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.
Subject(s)
Key words
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptor, EphA3 / Receptors, CCR10 / Idiopathic Pulmonary Fibrosis / Mesenchymal Stem Cells Limits: Animals / Humans Language: En Journal: JCI Insight Year: 2021 Document type: Article Affiliation country: United States
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptor, EphA3 / Receptors, CCR10 / Idiopathic Pulmonary Fibrosis / Mesenchymal Stem Cells Limits: Animals / Humans Language: En Journal: JCI Insight Year: 2021 Document type: Article Affiliation country: United States