Human CD34+/dim neutrophil-committed progenitors do not differentiate into neutrophil-like CXCR1+CD14+CD16- monocytes in vitro

The advent of recent cutting-edge technologies has allowed the discovery and characterization of novel progenitors of human neutrophils, including SSC(lo)CD66b(+)CD15(+)CD11b(-)CD49d(hi)proNeu1s, SSC(hi)CD66b(+)CD15(+)CD11b(-)CD49d(int)proNeus2s, CD66b(+)CD15(+)CD11b(+)CD49d(+)CD101(-)preNeus, and Lin(-)CD66b(+)CD117(+)CD71(+)eNePs. In this research field, we recently identified CD66b(-)CD38(+)CD64(dim)CD115(-), CD34(+), and CD34(dim/-) cells exclusively committed to the neutrophil lineage (which we renamed as CD34(+) and CD34(dim/-) neutrophil-committed progenitors), representing the earliest neutrophil precursors identifiable and sorted by flow cytometry. Moreover, based on their differential CD34 and CD45RA expression, we could identify 4 populations of neutrophil-committed progenitors: CD34(+)CD45RA(-)/NCP1s, CD34(+)CD45RA(+)/NCP2s, CD34(dim/-)CD45RA(+)/NCP3s, and CD34(dim/-)CD45RA(-)/NCP4s. This said, a very recent study by Ikeda and coworkers (PMID: 36862552) reported that neutrophil precursors, termed either neutrophil progenitors or "early neutrophil-committed progenitors," would generate immunosuppressive neutrophil-like CXCR1(+)CD14(+)CD16(-) monocytes. Hence, presuming that neutrophil progenitors/"early neutrophil-committed progenitors" correspond to neutrophil-committed progenitors, the selective neutrophil commitment that we attributed to neutrophil-committed progenitors is contradicted by Ikeda and coworkers' article. In this study, by performing a more analytical reevaluation at the phenotypic and molecular levels of the cells generated by neutrophil-committed progenitors 2 and 4 (selected as representatives of neutrophil-committed progenitors), we categorically exclude that neutrophil-committed progenitors generate neutrophil-like CXCR1(+)CD14(+)CD16(-) monocytes. Rather, we provide substantial evidence indicating that the cells generated by neutrophil progenitors/"early neutrophil-committed progenitors" are neutrophilic cells at a different stage of maturation, displaying moderate levels of CD14, instead of neutrophil-like CXCR1(+)CD14(+)CD16(-) monocytes, as pointed by Ikeda and coworkers. Hence, the conclusion that neutrophil progenitors/"early neutrophil-committed progenitors" aberrantly differentiate into neutrophil-like monocytes derives, in our opinion, from data misinterpretation.