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On the origin of neutrophils

Cellular & Molecular Immunology volume 22, pages 459–460 (2025)Cite this article

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The Original Article was published on 13 February 2025

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Neutrophils belong to the effector cells of the innate immune response to pathogens, tissue damage, and tumors [1]. The main origin of neutrophils in homeostasis is the bone marrow [2], although progenitor cells of neutrophils can be liberated from the bone marrow and can mature in distant tissues; this process is generally referred to as extramedullary neutropoiesis [3]. The latter process occurs particularly during immunological stress. Despite the consensus that neutrophils are the main innate immune cells in the peripheral blood, there is much debate in the literature concerning the mechanisms underlying their production in the bone marrow [4].

In this issue of  Cellular and Molecular Immunology, Signoretto and colleagues have expanded these studies by providing two important new findings: 1. The occurrence of two new NCPs, NCP5 and NCP6 (Fig. 1), and 2. data supporting the presence of multiple differentiation pathways that can be discriminated by the expression of CD45RA [7]. The differentiation pathway associated with the expression of CD45RA includes NCP2, NCP3 and NCP5, whereas the CD45RA-negative pathway comprises NCP1 and NCP4. Both of these pathways converge at CD45RA-negative NCP6, followed by the promyelocyte stage [7], which, according to the most recent in vitro data, appears to be the last stage that can proliferate [8]. Importantly, the pool sizes of NCPs are relatively small, making these cells rare in the total bone marrow pool [6, 7].

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Fig. 1

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  • 09 April 2025

    Bi-directional link was added.

References

  1. Hidalgo A, Chilvers ER, Summers C, Koenderman L. The neutrophil life cycle. Trends Immunol. 2019;40:584–97.

    Article  CAS  PubMed  Google Scholar 

  2. Overbeeke C, Tak T, Koenderman L. The journey of neutropoiesis: how complex landscapes in bone marrow guide continuous neutrophil lineage determination. Blood. 2022;139:2285–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Guo R, Xie X, Ren Q, Liew PX. New insights on extramedullary granulopoiesis and neutrophil heterogeneity in the spleen and its importance in disease. J Leukoc Biol. 2024;8:qiae220.

    Google Scholar 

  4. Koenderman L, Tesselaar K, Vrisekoop N. Human neutrophil kinetics: a call to revisit old evidence. Trends Immunol. 2022;43:868–76.

    Article  CAS  PubMed  Google Scholar 

  5. Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008;132:631–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Calzetti F, Finotti G, Tamassia N, Bianchetto-Aguilera F, Castellucci M, Canè S, et al. CD66b−CD64dimCD115− cells in the human bone marrow represent neutrophil-committed progenitors. Nat Immunol. 2022;23:679–91.

    Article  CAS  PubMed  Google Scholar 

  7. Signoretto I et al. Uncovering two neutrophil-committed progenitors that immediately precede the promyelocytes during human neutropoiesis. Cell Mol Immunol., 2025;22:316–29.

  8. Behbehani GK, Bendall SC, Clutter MR, Fantl WJ, Nolan GP. Single-cell mass cytometry adapted to measurements of the cell cycle. Cytometry Part A. 2012;81A:552–66.

    Article  Google Scholar 

  9. Potten CS, Schofield R, Lajtha LG. A comparison of cell replacement in bone marrow, testis and three regions of surface epithelium. BBA. Rev Cancer. 2 1979;560:281–99.

    CAS  Google Scholar 

  10. Lahoz-Beneytez J, Elemans M, Zhang Y, Ahmed R, Salam A, Block M, et al. Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives. Blood. 2016;127:3431–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands

    Leo Koenderman & Nienke Vrisekoop

  2. Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands

    Leo Koenderman, Kiki Tesselaar & Nienke Vrisekoop

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  1. Leo Koenderman
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  2. Kiki Tesselaar
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  3. Nienke Vrisekoop
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Correspondence to Leo Koenderman.

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Koenderman, L., Tesselaar, K. & Vrisekoop, N. On the origin of neutrophils. Cell Mol Immunol 22, 459–460 (2025). https://doi.org/10.1038/s41423-025-01270-1

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