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 hematopoietic progenitors, including SSCloCD66b + CD15 + CD11b-CD49dhiproNeu1 s and SSChiCD66b + CD15 + CD11b-CD49dintproNeus2 s, CD66b + CD15 + CD11b + CD49d + CD101-preNeus and Lin-CD66b + CD117 + CD71 + eNePs along human neutropoiesis. 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 (NCPs)], representing the earliest neutrophil precursors identifiable and sorted by flow cytometry. Moreover, based on their differential CD34 and CD45RA expression, we could identify four populations of NCPs, namely: CD34 + CD45RA-/NCP1 s, CD34 + CD45RA+/NCP2 s, CD34dim/-CD45RA+/NCP3 s and CD34dim/-CD45RA-/NCP4 s. This said, a very recent study by Ikeda and coworkers (PMID: 36862552) reported that neutrophil precursors termed either neutrophil progenitors (NePs) or "early neutrophil-committed progenitors" would generate immunosuppressive neutrophil-like CXCR1 + CD14 + CD16-monocytes. Hence, presuming that NePs/alias "early neutrophil-committed progenitors" correspond to NCPs, the selective neutrophil-commitment that we attributed to NCPs is contradicted by Ikeda and coworkers' paper. In this study, by performing a more analytical reevaluation at the phenotypic and molecular levels of the cells generated by NCP2 s and NCP4 s (selected as representatives of NCPs), we categorically exclude that NCPs generate neutrophil-like CXCR1 + CD14 + CD16-monocytes. Rather, we provide substantial evidence indicating that the cells generated by NePs/alias "early neutrophil-committed progenitors" are neutrophilic cells at 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 NePs/alias "early neutrophil-committed progenitors" aberrantly differentiate into neutrophil-like monocytes derives, in our opinion, from data misinterpretation.