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Tertiary lymphoid follicles are often found in the lungs of patients with severe COPD but sex-related differences have not been previously investigated. We determined the impact of female sex hormones on chronic cigarette smoke-induced expression of lymphoid aggregates in mice with COPD-like pathologies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Lymphoid aggregate counts, total aggregate cross-sectional area and foamy macrophage counts were determined morphometrically in male, female, and ovariectomized mice exposed to air or cigarette smoke for 6\u2009months. B-cell activating factor (BAFF) protein expression and markers of oxidative stress were evaluated in mouse lung tissues by immunofluorescence staining and gene expression analyses. Quantitative histology was performed on lung tissue sections of human COPD lungs to evaluate follicle formation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Lymphoid follicle and foamy macrophage counts as well as the total follicle cross-sectional area were differentially increased in lung tissues of female mice compared to male mice, and these differences were abolished by ovariectomy. These lymphoid aggregates were positive for CD45, CD20, CD21 and BAFF expression. Differential increases in <jats:italic>Mmp12 and Cxcl2<\/jats:italic> gene expression correlated with an increase in foamy macrophages in parenchymal tissues of female but not male mice after smoke exposure. Parenchymal tissues from female mice failed to induce antioxidant-related genes in response to smoke exposure, and this effect was restored by ovariectomy. 3-nitrotyrosine, a stable marker of oxidative stress, positively correlated with <jats:italic>Mmp12<\/jats:italic> and <jats:italic>Cxcl2<\/jats:italic> gene expression. Hydrogen peroxide induced BAFF protein in mouse macrophage cell line. In human lung tissues, female smokers with severe COPD demonstrated increased numbers of lymphoid follicles compared with males.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Chronic smoke exposure increases the risk of lymphoid aggregate formation in female mice compared with male mice, which is mediated female sex hormones and BAFF expression in an oxidative environment.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12931-020-1311-8","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T10:02:47Z","timestamp":1581069767000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Sex differences in lymphoid follicles in COPD airways"],"prefix":"10.1186","volume":"21","author":[{"given":"Anthony","family":"Tam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Tanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Churg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne L.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Hogg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0756-6643","authenticated-orcid":false,"given":"Don D.","family":"Sin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,7]]},"reference":[{"issue":"6","key":"1311_CR1","first-page":"1","volume":"61","author":"DL Hoyert","year":"2012","unstructured":"Hoyert DL, Xu J. 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N Engl J Med 2004). All the participants provided informed consent to participate in the original study.All animal procedures were approved by the University of British Columbia Animal Care Committee (A11\u20130149).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"(Not applicable)","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"DDS is a Tier 1 Canada Research Chair in COPD and holds the De Lazzari Family Chair at the Centre for Heart Lung Innovation.All other authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"46"}}