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Antibody-mediated depletion of CCR10(+)EphA3(+) cells ameliorates fibrosis in IPF
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 fr...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262321/ https://www.ncbi.nlm.nih.gov/pubmed/33945505 http://dx.doi.org/10.1172/jci.insight.141061 |
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author | 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. |
author_facet | 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. |
author_sort | Hohmann, Miriam S. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8262321 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-82623212021-07-13 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. JCI Insight Research Article 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. American Society for Clinical Investigation 2021-06-08 /pmc/articles/PMC8262321/ /pubmed/33945505 http://dx.doi.org/10.1172/jci.insight.141061 Text en © 2021 Hohmann et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article 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. Antibody-mediated depletion of CCR10(+)EphA3(+) cells ameliorates fibrosis in IPF |
title | Antibody-mediated depletion of CCR10(+)EphA3(+) cells ameliorates fibrosis in IPF |
title_full | Antibody-mediated depletion of CCR10(+)EphA3(+) cells ameliorates fibrosis in IPF |
title_fullStr | Antibody-mediated depletion of CCR10(+)EphA3(+) cells ameliorates fibrosis in IPF |
title_full_unstemmed | Antibody-mediated depletion of CCR10(+)EphA3(+) cells ameliorates fibrosis in IPF |
title_short | Antibody-mediated depletion of CCR10(+)EphA3(+) cells ameliorates fibrosis in IPF |
title_sort | antibody-mediated depletion of ccr10(+)epha3(+) cells ameliorates fibrosis in ipf |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262321/ https://www.ncbi.nlm.nih.gov/pubmed/33945505 http://dx.doi.org/10.1172/jci.insight.141061 |
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