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Neutrophil chemoattractant receptors in health and disease: double-edged swords

Cellular & Molecular Immunology volume 17, pages 433–450 (2020)Cite this article

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Abstract

Neutrophils are frontline cells of the innate immune system. These effector leukocytes are equipped with intriguing antimicrobial machinery and consequently display high cytotoxic potential. Accurate neutrophil recruitment is essential to combat microbes and to restore homeostasis, for inflammation modulation and resolution, wound healing and tissue repair. After fulfilling the appropriate effector functions, however, dampening neutrophil activation and infiltration is crucial to prevent damage to the host. In humans, chemoattractant molecules can be categorized into four biochemical families, i.e., chemotactic lipids, formyl peptides, complement anaphylatoxins and chemokines. They are critically involved in the tight regulation of neutrophil bone marrow storage and egress and in spatial and temporal neutrophil trafficking between organs. Chemoattractants function by activating dedicated heptahelical G protein-coupled receptors (GPCRs). In addition, emerging evidence suggests an important role for atypical chemoattractant receptors (ACKRs) that do not couple to G proteins in fine-tuning neutrophil migratory and functional responses. The expression levels of chemoattractant receptors are dependent on the level of neutrophil maturation and state of activation, with a pivotal modulatory role for the (inflammatory) environment. Here, we provide an overview of chemoattractant receptors expressed by neutrophils in health and disease. Depending on the (patho)physiological context, specific chemoattractant receptors may be up- or downregulated on distinct neutrophil subsets with beneficial or detrimental consequences, thus opening new windows for the identification of disease biomarkers and potential drug targets.

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Acknowledgements

This research was supported by the Research Foundation - Flanders (FWO-Vlaanderen) (G.0808.18N), the European Union’s Horizon 2020 research and innovation program ImmunoAID under grant agreement No 779295 and a “C1” grant (C16/17/010) from KU Leuven. M.M. obtained a PhD fellowship supported by the L’Oréal-UNESCO for Women in Science initiative and the FWO-Vlaanderen. M.G. is a research expert funded by the Rega Foundation.

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  1. Laboratory of Molecular Immunology, Rega Institute, KU Leuven, Herestraat 49 bus 1042, B-3000, Leuven, Belgium

    Mieke Metzemaekers, Mieke Gouwy & Paul Proost

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  1. Mieke Metzemaekers
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  2. Mieke Gouwy
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  3. Paul Proost
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M.M. wrote the initial manuscript, which was corrected and modified by M.G. and P.P. All authors approved the final version of the manuscript.

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Correspondence to Paul Proost.

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Metzemaekers, M., Gouwy, M. & Proost, P. Neutrophil chemoattractant receptors in health and disease: double-edged swords. Cell Mol Immunol 17, 433–450 (2020). https://doi.org/10.1038/s41423-020-0412-0

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  • DOI: https://doi.org/10.1038/s41423-020-0412-0

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