Marco A Cassatella

The advent of recent cutting-edge technologies has allowed the discovery and characterization of novel progenitors of human neutrophils, including SSCloCD66b+CD15+CD11b−CD49dhiproNeu1s, SSChiCD66b+CD15+CD11b−CD49dintproNeus2s, CD66b+CD15+CD11b+CD49d+CD101−preNeus, and Lin−CD66b+CD117+CD71+eNePs. In this research field, we recently identified CD66b−CD38+CD64dimCD115−, CD34+, and CD34dim/− cells exclusively committed to the neutrophil lineage (which we renamed as CD34+ and CD34dim/− 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, CD34dim/−CD45RA+/NCP3s, and CD34dim/−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.