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In this study, we revealed that a novel pore-forming protein ninjurin-1 (NINJ1) was highly expressed in pro-inflammatory neutrophil subpopulations during ALI, using public single-cell RNA sequencing and hotspot analysis. Furthermore, we demonstrated that the NINJ1 oligomerization was essential for the NET release in neutrophils from both acute respiratory distress syndrome (ARDS) patients and ALI mice. Genetic ablation of\n                    <jats:italic>Ninj1<\/jats:italic>\n                    in neutrophils abolished NET release, thereby attenuating pulmonary dysfunction and reducing ALI-related lethality. Mechanistically, we found that K45 and N60 are critical for NINJ1 oligomerization and subsequent NET release. In summary, our findings reveal a novel pore-forming protein-mediated mechanism for NET release and highlight NINJ1 as a potential therapeutic target for the treatment of ALI\/ARDS.\n                  <\/jats:p>","DOI":"10.1038\/s41419-026-08995-5","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T12:14:11Z","timestamp":1782389651000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["NINJ1 plays a vital role in the release of neutrophil extracellular traps during acute lung injury"],"prefix":"10.1038","volume":"17","author":[{"given":"Wen-Jing","family":"Zhong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Biao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Rui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan-Shi-Yu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Bing","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Feng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8505-8724","authenticated-orcid":false,"given":"Cha-Xiang","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Feng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Xi","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7348-2376","authenticated-orcid":false,"given":"Yong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"8995_CR1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1164\/rccm.202303-0558WS","volume":"209","author":"MA Matthay","year":"2024","unstructured":"Matthay MA, Arabi Y, Arroliga AC, Bernard G, Bersten AD, Brochard LJ, et al. 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Human neutrophils were obtained from ARDS patients undergoing thoracic surgery at Xiangya Hospital of Central South University (Changsha, China). Patients included both those diagnosed with ARDS and those without ARDS. Informed consent was obtained from all participants, and the study was approved by the Clinical Medical Ethics Committee of Xiangya Hospital, Central South University (Approval No. 2024030484).","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"787"}}