Hypoxia-inducible factor-dependent induction of myeloid-derived netrin-1 attenuates natural killer cell infiltration during endotoxin-induced lung injury

Authors

Nathaniel K Berg
Jiwen Li
Boyun Kim
Tingting Mills
Guangsheng Pei
Zhongming Zhao
Xiangyun Li
Xu Zhang
Wei Ruan
Holger K Eltzschig
Xiaoyi Yuan

Publication Date

4-1-2021

Journal

The FASEB Journal

Abstract

Sepsis and sepsis-associated lung inflammation significantly contribute to the morbidity and mortality of critical illness. Here, we examined the hypothesis that neuronal guidance proteins could orchestrate inflammatory events during endotoxin-induced lung injury. Through a targeted array, we identified netrin-1 as the top upregulated neuronal guidance protein in macrophages treated with lipopolysaccharide (LPS). Furthermore, we found that netrin-1 is highly enriched in infiltrating myeloid cells, particularly in macrophages during LPS-induced lung injury. Transcriptional studies implicate hypoxia-inducible factor HIF-1α in the transcriptional induction of netrin-1 during LPS treatment. Subsequently, the deletion of netrin-1 in the myeloid compartment (Ntn1

Keywords

Animals, Chemokine CCL2, Cytokines, Endotoxins, Gene Expression Regulation, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Killer Cells, Natural, Lung, Lung Injury, Macrophages, Mice, Mice, Inbred Strains, Myeloid Cells, Netrin-1, Neutrophils, Up-Regulation