{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:07:25Z","timestamp":1791086845549,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,12,4]],"date-time":"2012-12-04T00:00:00Z","timestamp":1354579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:p>Asthma is a chronic inflammatory disease of the lung with airflow obstruction and bronchospasm, characterized by pulmonary eosinophilia, airway remodeling, increased airway hyperresponsiveness to environmental stimuli, and excessive <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>h2\u2010type cytokine production. Recent studies indicate that crosstalk between the innate and adaptive immune systems is crucial for this disease. We and others have showed that the <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ok (downstream of tyrosine kinases) family adaptors, <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ok\u20101, <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ok\u20102, and <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ok\u20103, play essential roles in negative regulation of a wide variety of signaling pathways in both innate and adaptive immunities. Here, histopathology and bronchoalveolar lavage fluid (<jats:styled-content style=\"fixed-case\">BALF<\/jats:styled-content>) cellularity showed spontaneous pulmonary inflammation in <jats:italic><jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ok\u20101<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup><jats:italic><jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ok\u20102<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup><jats:italic><jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ok\u20103<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> (<jats:styled-content style=\"fixed-case\">TKO<\/jats:styled-content>) mice, but not in <jats:italic><jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ok\u20101<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup><jats:italic><jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ok\u20102<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> or <jats:italic><jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ok\u20103<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice, with hallmarks of asthma, including eosinophilia, goblet cell hyperplasia, and subepithelial fibrosis. Consistently, <jats:styled-content style=\"fixed-case\">TKO<\/jats:styled-content> mice, but not the other mutants, showed increased airway hyperresponsiveness to methacholine inhalation. In addition, <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>h2\u2010type cytokine concentrations in <jats:styled-content style=\"fixed-case\">BALF<\/jats:styled-content> were increased in <jats:styled-content style=\"fixed-case\">TKO<\/jats:styled-content> mice. These findings provide strong evidence that <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ok\u20101, <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ok\u20102, and <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ok\u20103 cooperatively play critical anti\u2010inflammatory roles in lung homeostasis.<\/jats:p>","DOI":"10.1111\/gtc.12016","type":"journal-article","created":{"date-parts":[[2012,12,4]],"date-time":"2012-12-04T19:37:37Z","timestamp":1354649857000},"page":"56-65","source":"Crossref","is-referenced-by-count":14,"title":["<scp>D<\/scp>ok adaptors play anti\u2010inflammatory roles in pulmonary homeostasis"],"prefix":"10.1111","volume":"18","author":[{"given":"Ryuichi","family":"Mashima","sequence":"first","affiliation":[{"name":"Division of Genetics The Institute of Medical Science The University of Tokyo 4\u20106\u20101 Shirokanedai Minato\u2010ku Tokyo 108\u20108639 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumimasa","family":"Arimura","sequence":"additional","affiliation":[{"name":"Division of Genetics The Institute of Medical Science The University of Tokyo 4\u20106\u20101 Shirokanedai Minato\u2010ku Tokyo 108\u20108639 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Kajikawa","sequence":"additional","affiliation":[{"name":"Division of Genetics The Institute of Medical Science The University of Tokyo 4\u20106\u20101 Shirokanedai Minato\u2010ku Tokyo 108\u20108639 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Pathology Tokyo Women's Medical University 8\u20101 Kawada\u2010cho Shinjuku\u2010ku Tokyo 162\u20108666 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Nakae","sequence":"additional","affiliation":[{"name":"Frontier Research Initiative The Institute of Medical Science The University of Tokyo 4\u20106\u20101 Shirokanedai Minato\u2010ku Tokyo 108\u20108639 Japan"},{"name":"Laboratory of Systems Biology Center for Experimental Medicine and Systems Biology The Institute of Medical Science The University of Tokyo 4\u20106\u20101 Shirokanedai Minato\u2010ku Tokyo 108\u20108639 Japan"},{"name":"Precursory Research for Embryonic Science and Technology (PRESTO) Japan Science and Technology Agency 4\u20101\u20108 Honcho Kawaguchi City Saitama 332\u20100012 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Yamanashi","sequence":"additional","affiliation":[{"name":"Division of Genetics The Institute of Medical Science The University of Tokyo 4\u20106\u20101 Shirokanedai Minato\u2010ku Tokyo 108\u20108639 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,12,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.527"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.12.040194.001455"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.5.9903102"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.4049\/jimmunol.147.9.2950","article-title":"Humoral immune functions in IL\u20104 transgenic mice","volume":"147","author":"Burstein H.J.","year":"1991","journal-title":"J. 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