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However, pathogenic mechanisms of AERD remain to be clarified. Here, we aimed to find the significance of transforming growth factor beta 1 (TGF-\u03b21) in association with cysteinyl leukotriene E<jats:sub>4<\/jats:sub>(LTE<jats:sub>4<\/jats:sub>) production, leading to eosinophil degranulation. To evaluate levels of serum TGF-\u03b21, first cohort enrolled AERD (n = 336), ATA (n = 442) patients and healthy control subjects (HCs, n = 253). In addition, second cohort recruited AERD (n = 34) and ATA (n = 25) patients to investigate a relation between levels of serum TGF-\u03b21 and urinary LTE<jats:sub>4<\/jats:sub>. The function of TGF-\u03b21 in LTE<jats:sub>4<\/jats:sub>production was further demonstrated by<jats:italic>ex vivo<\/jats:italic>(human peripheral eosinophils) or<jats:italic>in vivo<\/jats:italic>(BALB\/c mice) experiment. As a result, the levels of serum TGF-\u03b21 were significantly higher in AERD patients than in ATA patients or HCs (<jats:italic>P<\/jats:italic>= .001; respectively). Moreover, levels of serum TGF-\u03b21 and urinary LTE<jats:sub>4<\/jats:sub>had a positive correlation (<jats:italic>r<\/jats:italic>= 0.273,<jats:italic>P<\/jats:italic>= .037). In the presence of TGF-\u03b21, leukotriene C<jats:sub>4<\/jats:sub>synthase (LTC<jats:sub>4<\/jats:sub>S) expression was enhanced in peripheral eosinophils to produce LTE<jats:sub>4<\/jats:sub>, which sequentially induced eosinophil degranulation via the p38 pathway. When mice were treated with TGF-\u03b21, significantly induced eosinophilia with increased LTE<jats:sub>4<\/jats:sub>production in the lung tissues were noted. These findings suggest that higher levels of TGF-\u03b21 in AERD patients may contribute to LTE<jats:sub>4<\/jats:sub>production via enhancing LTC<jats:sub>4<\/jats:sub>S expression which induces eosinophil degranulation, accelerating airway inflammation.<\/jats:p>","DOI":"10.1371\/journal.pone.0256237","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T17:33:04Z","timestamp":1629999184000},"page":"e0256237","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of TGF-\u03b21 on eosinophils to induce cysteinyl leukotriene E4 production in aspirin-exacerbated respiratory disease"],"prefix":"10.1371","volume":"16","author":[{"given":"Youngwoo","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyoon","family":"Sim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Hyun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Ra","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga-Young","family":"Ban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoo Seob","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon-Keun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2614-0303","authenticated-orcid":true,"given":"Hae-Sim","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"issue":"3","key":"pone.0256237.ref001","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.jaci.2016.09.025","article-title":"Aspirin-exacerbated respiratory disease: Mediators and mechanisms of a clinical disease","volume":"139","author":"KN Cahill","year":"2017","journal-title":"J Allergy Clin Immunol"},{"issue":"4","key":"pone.0256237.ref002","doi-asserted-by":"crossref","first-page":"298","DOI":"10.4168\/aair.2016.8.4.298","article-title":"Update on the Management of Aspirin-Exacerbated Respiratory Disease","volume":"8","author":"KM Buchheit","year":"2016","journal-title":"Allergy Asthma Immunol Res"},{"issue":"2","key":"pone.0256237.ref003","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.alit.2015.01.004","article-title":"Association and management of eosinophilic inflammation in upper and lower airways","volume":"64","author":"M Okano","year":"2015","journal-title":"Allergol Int"},{"issue":"4","key":"pone.0256237.ref004","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.jaci.2016.04.042","article-title":"Eosinophil production of prostaglandin D2 in patients with aspirin-exacerbated respiratory disease","volume":"138","author":"X Feng","year":"2016","journal-title":"J Allergy Clin Immunol"},{"issue":"4","key":"pone.0256237.ref005","doi-asserted-by":"crossref","first-page":"823","DOI":"10.3904\/kjim.2020.022","article-title":"Distinct functions of eosinophils in severe asthma with type 2 phenotype: clinical implications","volume":"35","author":"Y Choi","year":"2020","journal-title":"Korean J Intern Med"},{"issue":"6","key":"pone.0256237.ref006","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1164\/rccm.201412-2278OC","article-title":"Cytokines in Chronic Rhinosinusitis. 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