Neutrophil Infiltration and Function in the Pathogenesis of Inflammatory Airspace Disease

Haynes, Maureen E.; Sullivan, David P.; Muller, William A.

doi:10.1016/j.ajpath.2023.12.008

The American Journal of Pathology

2024

DOI: 10.1016/j.ajpath.2023.12.008

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Neutrophil Infiltration and Function in the Pathogenesis of Inflammatory Airspace Disease

Maureen E. Haynes,

David P. Sullivan,

William A. Muller

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2024

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Endothelial ERG programs neutrophil transcriptome for sustained anti-inflammatory vascular niche

Vellingiri,

Balaji Ragunathrao,

Joshi

et al. 2024

Preprint

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Neutrophils (PMNs) reside as a marginated pool within the vasculature, ready for deployment during infection. However, how endothelial cells (ECs) control PMN extravasation and activation to strengthen tissue homeostasis remains ill -defined. Here, we found that the vascular ETS-related gene (ERG) is a generalized mechanism regulating PMN activity in preclinical tissue injury models and human patients. We show that ERG loss in ECs rewired PMN-transcriptome, enriched for genes associated with the CXCR2-CXCR4 signaling. Rewired PMNs compromise mice survival after pneumonia and induced lung vascular inflammatory injury following adoptive transfer into naive mice, indicating their longevity and inflammatory activity memory. Mechanistically, EC-ERG restricted PMN extravasation and activation by upregulating the deubiquitinase A20 and downregulating the NFκB-IL8 cascade. Rescuing A20 in EC-Erg-/- endothelium or suppressing PMN-CXCR2 signaling rescued EC control of PMN activation. Findings deepen our understanding of EC control of PMN-mediated inflammation, offering potential avenues for targeting various inflammatory diseases.

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Endothelial ERG programs neutrophil transcriptome for sustained anti-inflammatory vascular niche

Vellingiri,

Balaji Ragunathrao,

Joshi

et al. 2024

Preprint

View full text Add to dashboard Cite

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Neutrophil Infiltration and Function in the Pathogenesis of Inflammatory Airspace Disease

Cited by 1 publication

References 84 publications

Endothelial ERG programs neutrophil transcriptome for sustained anti-inflammatory vascular niche

Endothelial ERG programs neutrophil transcriptome for sustained anti-inflammatory vascular niche

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