TY - JOUR AU - Hohmann, Miriam S. AU - Habiel, David M. AU - Espindola, Milena S. AU - Huang, Guanling AU - Jones, Isabelle AU - Narayanan, Rohan AU - Coelho, Ana Lucia AU - Oldham, Justin M. AU - Noth, Imre AU - Ma, Shwu-Fan AU - Kurkciyan, Adrianne AU - McQualter, Jonathan L. AU - Carraro, Gianni AU - Stripp, Barry AU - Chen, Peter AU - Jiang, Dianhua AU - Noble, Paul W. AU - Parks, William AU - Woronicz, John AU - Yarranton, Geoffrey AU - Murray, Lynne A. AU - Hogaboam, Cory M. T1 - Antibody-mediated depletion of CCR10+EphA3+ cells ameliorates fibrosis in IPF PY - 2021/06/08/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.141061 VL - 6 IS - 11 UR - https://doi.org/10.1172/jci.insight.141061 PB - The American Society for Clinical Investigation ER -