{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:38:45Z","timestamp":1790249925007,"version":"4.1.0"},"reference-count":83,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Allergic asthma is a chronic Th2 inflammation in the lungs that constricts the airways and presents as coughing and wheezing. Asthma mostly affects boys in childhood and women in adulthood, suggesting that shifts in sex hormones alter the course of the disease. Alveolar macrophages have emerged as major mediators of allergic lung inflammation in animal models as well as humans. Whether sex differences exist in macrophage polarization and the molecular mechanism(s) that drive differential responses are not well understood. We found that IL-4\u2013stimulated bone marrow\u2013derived and alveolar macrophages from female mice exhibited greater expression of M2 genes in vitro and after allergen challenge in vivo. Alveolar macrophages from female mice exhibited greater expression of the IL-4R\u03b1 and estrogen receptor (ER) \u03b1 compared with macrophages from male mice following allergen challenge. An ER\u03b1-specific agonist enhanced IL-4\u2013induced M2 gene expression in macrophages from both sexes, but more so in macrophages from female mice. Furthermore, IL-4\u2013stimulated macrophages from female mice exhibited more transcriptionally active histone modifications at M2 gene promoters than did macrophages from male mice. We found that supplementation of estrogen into ovariectomized female mice enhanced M2 polarization in vivo upon challenge with allergen and that macrophage-specific deletion of ER\u03b1 impaired this M2 polarization. The effects of estrogen are long-lasting; bone marrow\u2013derived macrophages from ovariectomized mice implanted with estrogen exhibited enhanced IL-4\u2013induced M2 gene expression compared with macrophages from placebo-implanted littermates. Taken together, our findings suggest that estrogen enhances IL-4\u2013induced M2 gene expression and thereby contributes to sex differences observed in asthma.<\/jats:p>","DOI":"10.4049\/jimmunol.1601975","type":"journal-article","created":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T20:40:24Z","timestamp":1501533624000},"page":"1573-1583","source":"Crossref","is-referenced-by-count":164,"title":["Estrogen Signaling Contributes to Sex Differences in Macrophage Polarization during Asthma"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1379-2716","authenticated-orcid":false,"given":"Aleksander","family":"Keselman","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine , Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine , Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6486-1676","authenticated-orcid":false,"given":"Preston B","family":"White","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine , Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7247-2021","authenticated-orcid":false,"given":"Nicola M","family":"Heller","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine , Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,9,1]]},"reference":[{"key":"2025030614272151500_r1","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1398-9995.2004.00526.x","article-title":"The global burden of asthma: executive summary of the GINA dissemination committee report","volume":"59","author":"Masoli","year":"2004","journal-title":"Allergy"},{"key":"2025030614272151500_r2","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/j.1399-3038.2008.00805.x","article-title":"The association of allergic symptoms with sensitization to inhalant allergens in childhood","volume":"20","author":"Govaere","year":"2009","journal-title":"Pediatr. 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