{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T12:43:27Z","timestamp":1785156207774,"version":"3.55.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"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":[[2017,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>EBI3 functions as the subunit of immune-regulatory cytokines, such as IL-27 and IL-35, by pairing with p28 and p35, respectively. We treated wild-type and EBI3-deficient mice with intratracheal administration of LPS and obtained bronchoalveolar lavage fluid (BALF) 24 h later. Although neutrophils were the predominant cells in BALF from both groups of mice, eosinophils were highly enriched and there was increased production of eosinophil-attracting chemokines CCL11 and CCL24 in BALF of EBI3-deficient mice. The bronchial epithelial cells and alveolar macrophages were the major producers of CCL11 and CCL24. Because no such increases in eosinophils were seen in BALF of p28\/IL-27\u2013deficient mice or WSX-1\/IL-27R\u03b1 subunit-deficient mice upon intratracheal stimulation with LPS, we considered that the lack of IL-35 was responsible for the enhanced airway eosinophilia in EBI3-deficient mice. In vitro, IL-35 potently suppressed production of CCL11 and CCL24 by human lung epithelial cell lines treated with TNF-\u03b1 and IL-1\u03b2. IL-35 also suppressed phosphorylation of STAT1 and STAT3 and induced suppressor of cytokine signaling 3. In vivo, rIL-35 dramatically reduced LPS-induced airway eosinophilia in EBI3-deficient mice, with concomitant reduction of CCL11 and CCL24, whereas neutralization of IL-35 significantly increased airway eosinophils in LPS-treated wild-type mice. Collectively, our results suggest that IL-35 negatively regulates airway eosinophilia, at least in part by reducing the production of CCL11 and CCL24.<\/jats:p>","DOI":"10.4049\/jimmunol.1600506","type":"journal-article","created":{"date-parts":[[2016,11,24]],"date-time":"2016-11-24T02:50:22Z","timestamp":1479955822000},"page":"119-127","source":"Crossref","is-referenced-by-count":31,"title":["IL-35 Suppresses Lipopolysaccharide-Induced Airway Eosinophilia in EBI3-Deficient Mice"],"prefix":"10.1093","volume":"198","author":[{"given":"Kyosuke","family":"Kanai","sequence":"first","affiliation":[{"name":"Department of Microbiology, Kindai University Faculty of Medicine , Osaka 589-8511,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ah-Mee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kindai University Faculty of Medicine , Osaka 589-8511,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Saga University Faculty of Medicine , Saga 840-8502,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-714X","authenticated-orcid":false,"given":"Ikuo","family":"Tsunoda","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kindai University Faculty of Medicine , Osaka 589-8511,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Yoshie","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kindai University Faculty of Medicine , Osaka 589-8511,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,1,1]]},"reference":[{"key":"2025030614573405200_r1","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/ni.2366","article-title":"IL-12 family cytokines: immunological playmakers","volume":"13","author":"Vignali","year":"2012","journal-title":"Nat. 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