AUTHOR=Delobel Pauline , Ginter Benjamin , Rubio Eliane , Balabanian Karl , Lazennec Gwendal 

TITLE=CXCR2 intrinsically drives the maturation and function of neutrophils in mice

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1005551

DOI=10.3389/fimmu.2022.1005551

ISSN=1664-3224

ABSTRACT=<p>Neutrophils play a major role in the protection from infections but also in inflammation related to tumor microenvironment. However, cell-extrinsic and -intrinsic cues driving their function at steady state is still fragmentary. Using <italic>Cxcr2</italic> knock-out mice, we have evaluated the function of the chemokine receptor Cxcr2 in neutrophil physiology. We show here that Cxcr2 deficiency decreases the percentage of mature neutrophils in the spleen, but not in the bone marrow (BM). There is also an increase of aged CD62L<sup>lo</sup> CXCR4<sup>hi</sup> neutrophils in the spleen of KO animals. Spleen <italic>Cxcr2<sup>-/-</sup></italic> neutrophils display a reduced phagocytic ability, whereas BM neutrophils show an enhanced phagocytic ability compared to WT neutrophils. Spleen <italic>Cxcr2<sup>-/-</sup></italic> neutrophils show reduced reactive oxygen species production, F-actin and α-tubulin levels. Moreover, spleen <italic>Cxcr2<sup>-/-</sup></italic> neutrophils display an altered signaling with reduced phosphorylation of ERK1/2 and p38 MAPK, impaired PI3K-AKT, NF-κB, TGFβ and IFNγ pathways. Altogether, these results suggest that Cxcr2 is essential for neutrophil physiology.</p>