{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:43:51Z","timestamp":1787013831667,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T00:00:00Z","timestamp":1541376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002590","name":"American Lung Association","doi-asserted-by":"publisher","award":["RG\u2010416620"],"award-info":[{"award-number":["RG\u2010416620"]}],"id":[{"id":"10.13039\/100002590","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL075557"],"award-info":[{"award-number":["R01HL075557"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL137224"],"award-info":[{"award-number":["R01HL137224"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01HL126852"],"award-info":[{"award-number":["5R01HL126852"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The pathogenesis of asthma and airway obstruction is the result of an abnormal response to different environmental exposures. The scientific premise of our study was based on the finding that FoxO1 expression is increased in lung macrophages of mice after allergen exposure and human asthmatic patients. Macrophages are capable of switching from one functional phenotype to another, and it is important to understand the mechanisms involved in the transformation of macrophages and how their cellular function affects the peribronchial stromal microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We employed a murine asthma model, in which mice were treated by intranasal insufflation with allergens for 2\u20108\u00a0weeks. We used both a pharmacologic approach using a highly specific FoxO1 inhibitor and genetic approaches using FoxO1 knockout mice (FoxO1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      LysMcre). Cytokine level in biological fluids was measured by\n                      <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>\n                      and the expression of encoding molecules by NanoString assay and\n                      <jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We show that the levels of FoxO1 gene are significantly elevated in the airway macrophages of patients with mild asthma in response to subsegmental bronchial allergen challenge. Transcription factor FoxO1 regulates a pro\u2010asthmatic phenotype of lung macrophages that is involved in the development and progression of chronic allergic airway disease. We have shown that inhibition of FoxO1 induced phenotypic conversion of lung macrophages and downregulates pro\u2010asthmatic and pro\u2010fibrotic gene expression by macrophages, which contribute to airway inflammation and airway remodeling in allergic asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Targeting FoxO1 with its downstream regulator\n                      <jats:styled-content style=\"fixed-case\">IRF<\/jats:styled-content>\n                      4 is a novel therapeutic target for controlling allergic inflammation and potentially reversing fibrotic airway remodeling.\n                    <\/jats:p>\n                  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