{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:30:48Z","timestamp":1792467048625,"version":"4.5.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T00:00:00Z","timestamp":1639440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Neutrophil cytosolic factor 1 (<jats:italic>Ncf1<\/jats:italic>) is a major genetic factor associated with autoimmune diseases and has been identified as a key player in autoimmune mediated inflammation. We addressed the role of<jats:italic>Ncf1<\/jats:italic>in an antigen-induced pulmonary inflammation model, and found that the<jats:italic>Ncf1<jats:sup>m1j<\/jats:sup><\/jats:italic>mutation, causing a deficient reactive oxygen species response, alleviated disease. The<jats:italic>Ncf1<jats:sup>m1j<\/jats:sup><\/jats:italic>mutation was associated with a reduced inflammatory cell infiltration in airways, but had limited effect on mucus secretion, antibody production and lung fibrosis. The disease remission in the<jats:italic>Ncf1<\/jats:italic>mutated mice was reversed when functional<jats:italic>Ncf1<\/jats:italic>was transgenically expressed in alveolar macrophages, suggesting that the cellular inflammation was depended on functional<jats:italic>Ncf1<\/jats:italic>in alveolar macrophages. By determining cytokine and chemokine profiles in lung and serum, we found that<jats:italic>Ncf1<\/jats:italic>deficiency allowed an increased expression of Th1 cytokines, including TNF-\u03b1, IFN-\u03b3 and IL-12. Since also epithelial cytokines were found to be regulated by<jats:italic>Ncf1<\/jats:italic>, we tested the effect of<jats:italic>Ncf1<\/jats:italic>in IL-33 and IL-25 induced lung inflammation models. Mice with the<jats:italic>Ncf1<jats:sup>m1j<\/jats:sup><\/jats:italic>mutation showed less sensitivity to IL-33, but not IL-25, induced lung inflammation, in a macrophage independent manner. The mice with deficient<jats:italic>Ncf1<\/jats:italic>showed a reduced eosinophil infiltration and group 2 innate lymphoid cell (ILC2) activation. The production of IFN-\u03b3 in CD4<jats:sup>+<\/jats:sup>T cells was increased, whereas IL-5 and IL-13 in ILC2 were decreased. Importantly, anti-IFN-\u03b3 antibody treatment of<jats:italic>Ncf1<\/jats:italic>deficient mice increased eosinophil infiltration and rescued ILC2 activation in the lung. We conclude that<jats:italic>Ncf1<\/jats:italic>deficiency enhances Th1 response, deactivates ILC2, and protects against pulmonitis.<\/jats:p>","DOI":"10.3389\/fimmu.2021.783944","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T08:43:02Z","timestamp":1639471382000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Ncf1 Governs Immune Niches in the Lung to Mediate Pulmonary Inflammation in 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