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Nature: Neonatal imprinting of alveolar macrophages via neutrophil-derived 12-HETE

作者:   发布于:2023年08月27日  点击量:551
Title:

Neonatal imprinting of alveolar macrophages via neutrophil-derived 12-HETE

Journal:Nature
volume
Year:2023
Abstract:

Resident-tissue macrophages (RTMs) arise from embryonic precursors1,2, yet the developmental signals that shape their longevity remain largely unknown. Here we demonstrate in mice genetically deficient in 12-lipoxygenase and 15-lipoxygenase (Alox15−/− mice) that neonatal neutrophil-derived 12-HETE is required for self-renewal and maintenance of alveolar macrophages (AMs) during lung development. Although the seeding and differentiation of AM progenitors remained intact, the absence of 12-HETE led to a significant reduction in AMs in adult lungs and enhanced senescence owing to increased prostaglandin E2 production. A compromised AM compartment resulted in increased susceptibility to acute lung injury induced by lipopolysaccharide and to pulmonary infections with influenza A virus or SARS-CoV-2. Our results highlight the complexity of prenatal RTM programming and reveal their dependency on in trans eicosanoid production by neutrophils for lifelong self-renewal.

Cite/Figure:

Nature-2023-614-product-cited

Nature-2023-614-data-cited

Links:

https://www.nature.com/articles/s41586-022-05660-7(如需全文,请联系我们)