{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:39:38Z","timestamp":1792431578289,"version":"4.5.0"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,12,20]],"date-time":"2018-12-20T00:00:00Z","timestamp":1545264000000},"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>\n                    Asthma is a chronic inflammatory disease of airways mediated by T-helper 2 (Th2) cells involving complex signaling pathways. Although resveratrol has previously been shown to attenuate allergic asthma, the role of miRNA in this process has not been studied. We investigated the effect of resveratrol on ovalbumin-induced experimental allergic asthma in mice. To that end, BALB\/c mice were immunized with ovalbumin (OVA) intraperitoneally followed by oral gavage of vehicle (OVA-veh) or resveratrol (100 mg\/kg body) (OVA-res). On day 7, the experimental groups received intranasal challenge of OVA followed by 7 days of additional oral gavage of vehicle or resveratrol. At day 15, all mice were euthanized and bronchioalveolar fluid (BALF), serum and lung infiltrating cells were collected and analyzed. The data showed that resveratrol significantly reduced IL-5, IL-13, and TGF-\u03b2 in the serum and BALF in mice with OVA-induced asthma. Also, we saw a decrease in CD3+CD4+, CD3+CD8+, and CD4+IL-4+ cells with increase in CD4+CD25+FOXP3+ cells in pulmonary inflammatory cell infiltrate in OVA-res group when compared to OVA-veh. miRNA expression arrays using lung infiltrating cells showed that resveratrol caused significant alterations in miRNA expression, specifically downregulating the expression of miR-34a. Additionally, miR-34a was found to target\n                    <jats:italic>FOXP3<\/jats:italic>\n                    , as evidenced by enhanced expression of\n                    <jats:italic>FOXP3<\/jats:italic>\n                    in the lung tissue. Also, transfection studies showed that miR-34a inhibitor upregulated\n                    <jats:italic>FOXP3<\/jats:italic>\n                    expression while miR-34a-mimic downregulated\n                    <jats:italic>FOXP3<\/jats:italic>\n                    expression. The current study suggests that resveratrol attenuates allergic asthma by downregulating miR-34a that induces increased expression of\n                    <jats:italic>FOXP3<\/jats:italic>\n                    , a master regulator of Treg development and functions.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2018.02992","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T23:32:17Z","timestamp":1545262337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":87,"title":["Resveratrol Attenuates Allergic Asthma and Associated Inflammation in the Lungs Through Regulation of miRNA-34a That Targets FoxP3 in Mice"],"prefix":"10.3389","volume":"9","author":[{"given":"Esraah","family":"Alharris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Alghetaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratanesh","family":"Seth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Chatterjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narendra P.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitzi","family":"Nagarkatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash","family":"Nagarkatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,12,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/nri2254","article-title":"Immunology of asthma and chronic obstructive pulmonary disease","volume":"8","author":"Barnes","year":"2008","journal-title":"Nat Rev Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"S18","DOI":"10.1164\/ajrccm\/150.5_Pt_2.S18","article-title":"Mucosal inflammation and asthma","author":"Howarth","year":"1994","journal-title":"Am J Respir Crit Care Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1086\/317537","article-title":"Type 1\/Type 2 immunity in infectious diseases","volume":"32","author":"Spellberg","year":"2001","journal-title":"Clin Infect Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1067\/mai.2003.1557","article-title":"Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-beta, IL-11, IL-17, and type I and type III collagen expression","volume":"111","author":"Chakir","year":"2003","journal-title":"J Allergy Clin Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1016\/j.jaci.2004.07.014","article-title":"Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma","volume":"114","author":"Karagiannidis","year":"2004","journal-title":"J Allergy Clin Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/nri2343","article-title":"How regulatory T cells work","volume":"8","author":"Vignali","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1146\/annurev.immunol.21.120601.141122","article-title":"Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses","volume":"22","author":"Sakaguchi","year":"2004","journal-title":"Annu Rev Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1111\/j.1398-9995.2009.02056.x","article-title":"Decreased FOXP3 protein expression in patients with asthma","volume":"64","author":"Provoost","year":"2009","journal-title":"Allergy"},{"key":"B9","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/83713","article-title":"The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3","volume":"27","author":"Bennett","year":"2001","journal-title":"Nat Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1126\/science.275.5297.218","article-title":"Cancer chemopreventive activity of resveratrol, a natural product derived from grapes","volume":"275","author":"Jang","year":"1997","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","first-page":"4848","DOI":"10.4049\/jimmunol.165.9.4848","article-title":"T regulatory cells 1 inhibit a Th2-specific response in vivo. 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