{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T23:02:52Z","timestamp":1787526172416,"version":"build-2736575974"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T00:00:00Z","timestamp":1612310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Rationale<\/jats:title><jats:p>Severe eosinophilic asthma is characterized by airway eosinophilia and corticosteroid\u2010resistance, commonly overlapping with type 2 inflammation. It has been reported that chemokine (C\u2010C motif) ligand 5 (CCL5) is involved in the exacerbation of asthma by RNA virus infections. Indeed, treatment with a virus\u2010associated ligand and a T helper type 2 cell (Th2) cytokine can synergistically stimulate CCL5 production in bronchial epithelial cells. We aimed to evaluate the mechanisms underlying CCL5 production in this in vitro model and to assess the potential of Janus kinase 1 (JAK1) as a novel therapeutic target via the use of ruxolitinib.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We stimulated primary normal human bronchial epithelial (NHBE) cells and BEAS\u20102B cells with poly(I:C) along with interleukin\u201013 (IL\u201013) or IL\u20104, and assessed CCL5 production. We also evaluated the signals involved in virus\u2010 and Th2\u2010cytokine\u2010induced CCL5 production and explored a therapeutic agent that attenuates the CCL5 production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Poly(I:C) stimulated NHBE and BEAS\u20102B cells to produce CCL5. Poly(I:C) and IL\u201013 increased CCL5 production. Poly(I:C)\u2010induced CCL5 production occurred via the TLR3\u2013IRF3 and IFNAR\/JAK1\u2013phosphoinositide 3\u2010kinase (PI3K) pathways, but not the IFNAR\/JAK1\u2013STATs pathway. In addition, IL\u201013 did not augment poly(I:C)\u2010induced CCL5 production via the canonical IL\u201013R\/IL\u20104R\/JAK1\u2013STAT6 pathway but likely via subsequent TLR3\u2010IRF3\u2010IFNAR\/JAK1\u2010PI3K pathways. JAK1 was identified to be a potential therapeutic target for severe eosinophilic asthma. The JAK1\/2 inhibitor, ruxolitinib, was demonstrated to more effectively decrease CCL5 production in BEAS\u20102B cells than fluticasone propionate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We have demonstrated that JAK1 is a possible therapeutic target for severe corticosteroid\u2010resistant asthma with airway eosinophilia and persistent Th2\u2010type inflammation, and that ruxolitinib has potential as an alternative pharmacotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.397","type":"journal-article","created":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T14:47:44Z","timestamp":1612622864000},"page":"363-373","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Ruxolitinib inhibits poly(I:C) and type 2 cytokines\u2010induced CCL5 production in bronchial epithelial cells: A potential therapeutic agent for severe eosinophilic asthma"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1088-2954","authenticated-orcid":false,"given":"Mitsuru","family":"Sada","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Kyorin University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9988-5221","authenticated-orcid":false,"given":"Masato","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Kyorin University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiya","family":"Inui","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Kyorin University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7140-6273","authenticated-orcid":false,"given":"Keitaro","family":"Nakamoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Kyorin University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Kyorin University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masuo","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Kyorin University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kojiro","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Kyorin University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0502-8128","authenticated-orcid":false,"given":"Takeshi","family":"Saraya","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Kyorin University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Kurai","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of General Medicine, School of Medicine Kyorin University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Health Science Graduate School of Health Science, Gunma Paz University Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9435-9246","authenticated-orcid":false,"given":"Haruyuki","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Kyorin University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3207-8673","authenticated-orcid":false,"given":"Hajime","family":"Takizawa","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Kyorin University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,3]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Asthma GIf. 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