{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T18:54:43Z","timestamp":1762541683452},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,2,19]],"date-time":"2008-02-19T00:00:00Z","timestamp":1203379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Interleukin\u20101 receptor\u2010associated kinase (IRAK)\u20104 is a serine\u2010threonine kinase that plays an important role in innate and adaptive immune responses. While the requirement of IRAK\u20104 kinase activity has been studied in the context of IL\u20101R signaling, it is not clear whether IRAK\u20104 requires its kinase function for all of its roles in the immune system. IRAK\u20104 kinase\u2010dead knock\u2010in (IRAK\u20104KD\/KD) mice were generated to further elucidate whether IRAK\u20104 kinase activity is required for IRAK\u20104 to induce cytokine production. IRAK\u20104KD\/KD mice were impaired in their ability to produce cytokines in response to <jats:italic>in vivo<\/jats:italic> challenge with lipopolysaccharide (LPS), a potent TLR4 ligand. Cytokine production was also reduced in macrophages and dendritic cells from IRAK\u20104KD\/KD mice in response to LPS and other TLR ligands. In addition, adaptive immune responses were impaired in IRAK\u20104KD\/KD mice. Although <jats:italic>in vitro<\/jats:italic> T cell proliferation in response to TCR activation was unaffected in IRAK\u20104\u2010deficient mice, <jats:italic>in vivo<\/jats:italic> T cell responses to lymphocytic choriomeningitits virus infection were significantly impaired in IRAK\u20104\u2010knockout mice or mice expressing the kinase\u2010dead mutant of IRAK\u20104. Collectively, these results indicate that IRAK\u20104 kinase activity is required for IRAK\u20104\u2010dependent signaling in innate and adaptive immunity.<\/jats:p>","DOI":"10.1002\/eji.200737429","type":"journal-article","created":{"date-parts":[[2008,2,19]],"date-time":"2008-02-19T14:00:27Z","timestamp":1203429627000},"page":"870-876","source":"Crossref","is-referenced-by-count":32,"title":["IRAK\u20104 kinase activity is required for IRAK\u20104\u2010dependent innate and adaptive immune responses"],"prefix":"10.1002","volume":"38","author":[{"given":"Elizabeth","family":"Lye","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salim","family":"Dhanji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Calzascia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alisha R.","family":"Elford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela S.","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,2,19]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-32636-7_1"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.083001.084359"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/35066006"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst0280557"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2003.10.006"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00053-4"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402666200"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5252.1128"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/383443a0"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102262200"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.7.2475-2484.2001"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.10.5887"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01889"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087262"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.082100399"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5343.1612"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.27.19403"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.12.2073"},{"key":"e_1_2_7_19_2","doi-asserted-by":"crossref","first-page":"978","DOI":"10.4049\/jimmunol.163.2.978","article-title":"Impaired cytokine signaling in mice lacking the IL\u20101 receptor\u2010associated kinase.","volume":"163","author":"Thomas J. 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