{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T22:21:41Z","timestamp":1787955701012,"version":"build-2784847793"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"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":[[2016,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Airway epithelial cells are the major target for rhinovirus (RV) infection and express proinflammatory chemokines and antiviral cytokines that play a role in innate immunity. Previously, we demonstrated that RV interaction with TLR2 causes ILR-associated kinase-1 (IRAK-1) depletion in both airway epithelial cells and macrophages. Further, IRAK-1 degradation caused by TLR2 activation was shown to inhibit ssRNA-induced IFN expression in dendritic cells. Therefore, in this study, we examined the role of TLR2 and IRAK-1 in RV-induced IFN-\u03b2, IFN-\u03bb1, and CXCL-10, which require signaling by viral RNA. In airway epithelial cells, blocking TLR2 enhanced RV-induced expression of IFNs and CXCL-10. By contrast, IRAK-1 inhibition abrogated RV-induced expression of CXCL-10, but not IFNs in these cells. Neutralization of IL-33 or its receptor, ST2, which requires IRAK-1 for signaling, inhibited RV-stimulated CXCL-10 expression. In addition, RV induced expression of both ST2 and IL-33 in airway epithelial cells. In macrophages, however, RV-stimulated CXCL-10 expression was primarily dependent on TLR2\/IL-1R. Interestingly, in a mouse model of RV infection, blocking ST2 not only attenuated RV-induced CXCL-10, but also lung inflammation. Finally, influenza- and respiratory syncytial virus\u2013induced CXCL-10 was also found to be partially dependent on IL-33\/ST2\/IRAK-1 signaling in airway epithelial cells. Together, our results indicate that RV stimulates CXCL-10 expression via the IL-33\/ST2 signaling axis, and that TLR2 signaling limits RV-induced CXCL-10 via IRAK-1 depletion at least in airway epithelial cells. To our knowledge, this is the first report to demonstrate the role of respiratory virus\u2013induced IL-33 in the induction of CXCL-10 in airway epithelial cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1502702","type":"journal-article","created":{"date-parts":[[2016,8,9]],"date-time":"2016-08-09T02:23:08Z","timestamp":1470709388000},"page":"2409-2420","source":"Crossref","is-referenced-by-count":34,"title":["TLR2 Activation Limits Rhinovirus-Stimulated CXCL-10 by Attenuating IRAK-1\u2013Dependent IL-33 Receptor Signaling in Human Bronchial Epithelial Cells"],"prefix":"10.1093","volume":"197","author":[{"given":"Shyamala","family":"Ganesan","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0301-4216","authenticated-orcid":false,"given":"Duc","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxun","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9763-6544","authenticated-orcid":false,"given":"Mohammad","family":"Farazuddin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena H","family":"Hudy","sequence":"additional","affiliation":[{"name":"Department of Physiology & Pharmacology, University of Calgary Faculty of Medicine , Calgary, Alberta T2N 4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Unger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam T","family":"Comstock","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Proud","sequence":"additional","affiliation":[{"name":"Department of Physiology & Pharmacology, University of Calgary Faculty of Medicine , Calgary, Alberta T2N 4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S","family":"Lauring","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan , Ann Arbor, MI 48109"},{"name":"Department of Microbiology and Immunology, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma S","family":"Sajjan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,9,15]]},"reference":[{"key":"2025030617490203800_r1","first-page":"467","article-title":"Viral infections in exacerbations of asthma and chronic obstructive pulmonary disease","volume":"100","author":"Contoli","year":"2009","journal-title":"Minerva Med."},{"key":"2025030617490203800_r2","doi-asserted-by":"crossref","first-page":"116","DOI":"10.4168\/aair.2012.4.3.116","article-title":"Updates in the relationship between human rhinovirus and asthma","volume":"4","author":"Kim","year":"2012","journal-title":"Allergy Asthma Immunol. 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