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High iron levels have been commonly described in CF respiratory secretions. Af proteases cause a severe allergic immune response, leading to pulmonary exacerbations and progressive lung function decline. The stimuli that promote Af proteases in ABPA are poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Determine if airway iron is a critical factor in CF-ABPA by regulating fungal protease production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used transcriptomics and proteomics to investigate the role of iron in stimulating the production of Af proteases and evaluated the impact of these iron-induced Af proteases on the Th2 immune response in CF bronchial epithelial (CFBE) cells and in a CF-ABPA mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Transcriptional analysis showed a significant upregulation of Af proteases with exposure to iron and a downregulation with iron chelation. This finding was validated in secretome studies showing that Af-culture filtrates (Af-cf) from iron-exposed conidia contained significantly higher levels of 14 proteases compared to controls. Exposure to iron-primed Af-cf increased the production of Th2 promoting cytokines (IL-33, IL-25 and TSLP) in CFBE cells compared to the wild type cells. In vivo, inoculation of CF mice with iron-primed Af conidia led to higher levels of serum IgE and Th2 cytokines (IL-4, IL-5, IL-9, IL-13) in lung tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that airway iron is a potent stimulus for Af proteases and represents a modifiable risk factor and potential therapeutic target for CF-ABPA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1165\/rcmb.2025-0077oc","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T13:49:50Z","timestamp":1758203390000},"page":"229-240","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":2,"title":["Iron induces\n                    <i>Aspergillus<\/i>\n                    proteases in cystic fibrosis allergic bronchopulmonary 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