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Here, we examined the hypothesis that neuronal guidance proteins could orchestrate inflammatory events during endotoxin\u2010induced lung injury. Through a targeted array, we identified netrin\u20101 as the top upregulated neuronal guidance protein in macrophages treated with lipopolysaccharide (LPS). Furthermore, we found that netrin\u20101 is highly enriched in infiltrating myeloid cells, particularly in macrophages during LPS\u2010induced lung injury. Transcriptional studies implicate hypoxia\u2010inducible factor HIF\u20101\u03b1 in the transcriptional induction of netrin\u20101 during LPS treatment. Subsequently, the deletion of netrin\u20101 in the myeloid compartment (\n                    <jats:italic>\n                      Ntn1\n                      <jats:sup>loxp\/loxp<\/jats:sup>\n                    <\/jats:italic>\n                    LysM Cre) resulted in exaggerated mortality and lung inflammation. Surprisingly, further studies revealed enhanced natural killer cells (NK cells) infiltration in\n                    <jats:italic>\n                      Ntn1\n                      <jats:sup>loxp\/loxp<\/jats:sup>\n                    <\/jats:italic>\n                    LysM Cre mice, and neutralization of NK cell chemoattractant chemokine (C\u2010C motif) ligand 2 (CCL2) reversed the exaggerated lung inflammation. Together, these studies provide functional insight into myeloid cell\u2010derived netrin\u20101 in controlling lung inflammation through the modulation of CCL2\u2010dependent infiltration of NK cells.\n                  <\/jats:p>","DOI":"10.1096\/fj.202002407r","type":"journal-article","created":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T07:51:31Z","timestamp":1615708291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Hypoxia\u2010inducible factor\u2010dependent induction of myeloid\u2010derived netrin\u20101 attenuates natural killer cell infiltration during endotoxin\u2010induced lung injury"],"prefix":"10.1096","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2568-2867","authenticated-orcid":false,"given":"Nathaniel K.","family":"Berg","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, McGovern Medical School University of Texas Health Science Center Houston 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