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  • Perspective
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Strategies of neutrophil diversification

Nature Immunology volume 24, pages 575–584 (2023)Cite this article

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Abstract

Neutrophils are formidable defenders. Their vast numbers, constant production, high cytotoxicity and capacity to produce extracellular traps, underlie their ability to efficiently protect in a microorganism-rich world. However, neutrophils are much more than immune sentinels, as evidenced by the expanding repertoire of functions discovered in the context of tissue homeostasis, regeneration or chronic pathologies. In this Perspective, we discuss general functional features of the neutrophil compartment that may be relevant in most, if not all, physiological scenarios in which they participate, including specialization in naïve tissues, transcriptional noise in the bloodstream as a potential strategy for diversification and functional bias in inflammatory sites. We intentionally present the reader with more questions than answers and propose models and approaches that we hope will shed new light onto the biology of these fascinating cells and spark new directions of research.

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Fig. 1: Modeling the architecture of the neutrophil compartment.
Fig. 2: Mechanisms of diversification in blood.
Fig. 3: Transcriptional noise of neutrophils.
Fig. 4: Origin of behavioral states in blood.

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Acknowledgements

We thank members of the laboratory of A.H., P. Frenette, D. Lucas, L. Ng, G. Fernandez-Calvo, F. Sanchez-Cabo, M. Casanova-Acebes and J. M. Adrover for past and present discussion and inspiration on questions presented here. This manuscript has been possible through grants R01AI165661 from NIH/NIAD, RTI2018-095497-B-I00 from MCIN, HR17_00527 from Fundación La Caixa, the Transatlantic Network of Excellence (TNE-18CVD04) from the Leducq Foundation, and FET-OPEN (no. 861878) from the European Commission. M.P.-S. is supported by the EMBO ALTF (no. 1142-2020) long-term fellowship and from MICINN (RYC2021-033511-I). J.S. and I.B. are supported by fellowships from MICINN (PRE2019-089130 and RYC2020-029563-I, respectively). The CNIC is supported by the MCIN and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S).

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Authors and Affiliations

  1. Area of Cell & Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain

    Miguel Palomino-Segura, Jon Sicilia, Iván Ballesteros & Andrés Hidalgo

  2. Immunophysiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE) and Department of Physiology, Faculty of Sciences, University of Extremadura, Badajoz, Spain

    Miguel Palomino-Segura

  3. Vascular Biology and Therapeutics Program and Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA

    Andrés Hidalgo

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Palomino-Segura, M., Sicilia, J., Ballesteros, I. et al. Strategies of neutrophil diversification. Nat Immunol 24, 575–584 (2023). https://doi.org/10.1038/s41590-023-01452-x

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