AI Article Synopsis
- Idiopathic pulmonary fibrosis (IPF) involves abnormal lung tissue repair that worsens lung function, with the role of certain signaling molecules like CCR10 and CCL28 being highlighted in the disease process.
- Elevated levels of CCR10+ mesenchymal progenitor cells (MPCs) in IPF lungs contribute to fibrosis, as CCL28 stimulates their growth and depletion of CCR10 leads to cell death.
- Targeting EphA3 on CCR10+ cells with specific antibodies significantly reduces these cells and decreases lung fibrosis in animal models, suggesting a potential therapeutic approach for IPF.
Article 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262321 | PMC |
| http://dx.doi.org/10.1172/jci.insight.141061 | DOI Listing |
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