{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:49:36Z","timestamp":1775090976722,"version":"3.50.1"},"reference-count":78,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T00:00:00Z","timestamp":1490918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21 AI099430"],"award-info":[{"award-number":["R21 AI099430"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:p>Interleukin\u20101 receptor\u2010associated kinase (IRAK) 4 mediates host defense against infections. As an active kinase, IRAK4 elicits full spectra of myeloid differentiation primary response protein (MyD) 88\u2010dependent responses, while kinase\u2010inactive IRAK4 induces a subset of cytokines and negative regulators whose expression is not regulated by mRNA stability. IRAK4 kinase activity is critical for resistance against <jats:italic>Streptococcus pneumoniae<\/jats:italic>, but its involvement in autoimmunity is incompletely understood. In this study, we determined the role of IRAK4 kinase activity in murine lupus. Lupus development in BXSB mice expressing the Y chromosome autoimmunity accelerator (<jats:italic>Yaa<\/jats:italic>) increased basal and Toll\u2010like receptor (TLR) 4\/7\u2010induced phosphorylation of mitogen\u2010activated protein kinases, p65 nuclear factor\u2010\u03baB (NF\u2010\u03baB), enhanced tumor necrosis factor (TNF)\u2010\u03b1 and C\u2010C motif chemokine ligand (CCL) 5 gene expression in splenic macrophages, but decreased levels of Toll\u2010interacting protein and IRAK\u2010M, without affecting IRAK4 or IRAK1 expression. Mice harboring kinase\u2010inactive IRAK4 on the lupus\u2010prone <jats:italic>Yaa<\/jats:italic> background manifested blunted TLR signaling in macrophages and reduced glomerulonephritis, splenomegaly, serum anti\u2010nuclear antibodies, numbers of splenic macrophages, total and TNF\u2010\u03b1<jats:sup>+<\/jats:sup> dendritic cells, activated T\u2010 and B\u2010lymphocytes, and lower TNF\u2010\u03b1 expression in macrophages compared with lupus\u2010prone mice with functional IRAK4. Thus, IRAK4 kinase activity contributes to murine lupus and could represent a new therapeutic target.<\/jats:p>","DOI":"10.1002\/eji.201646641","type":"journal-article","created":{"date-parts":[[2017,3,10]],"date-time":"2017-03-10T08:45:51Z","timestamp":1489135551000},"page":"880-891","source":"Crossref","is-referenced-by-count":20,"title":["Deficiency in IRAK4 activity attenuates manifestations of murine Lupus"],"prefix":"10.1002","volume":"47","author":[{"given":"Michael","family":"Murphy","sequence":"first","affiliation":[{"name":"Department of Immunology University of Connecticut Health Center  Farmington CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goutham","family":"Pattabiraman","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Connecticut Health Center  Farmington CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tissa T.","family":"Manavalan","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Connecticut Health Center  Farmington CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei E.","family":"Medvedev","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Connecticut Health Center  Farmington CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,31]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12019-006-0006-5"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.160.1.51"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203314556139"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2014.11.007"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914902107"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000430251"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1300617110"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2014.10.010"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2010.06.009"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80412-2"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/mi.3.8.466"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3446"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838161"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804779200"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03646.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3277"},{"key":"e_1_2_7_18_1","first-page":"397","article-title":"Association of TLR9 gene polymorphisms with lupus nephritis in a Chinese Han population","volume":"28","author":"Zhou X. J.","year":"2010","journal-title":"Clin. Exp. Rheumatol"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.07.013"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.07.014"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124978"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603912103"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.09.009"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202195"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838138"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002242"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905441106"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300683"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.11.017"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22571"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901181106"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00827-9"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2011.155515"},{"key":"e_1_2_7_34_1","first-page":"375","article-title":"Association of interferon gamma, tumor necrosis factor alpha and interleukin 6 serum levels with systemic lupus erythematosus activity","volume":"46","author":"Robak E.","year":"1998","journal-title":"Arch. Immunol. Ther. Exp. (Warsz)"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-010-1761-2"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-010-9470-x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1159\/000430251"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.640128"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.2VMA0515-229RR"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3599"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0611273"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109537200"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12298"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.082100399"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-015-0067-7"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.8.5264"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102151"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep20373"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-010-1654-4"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00031"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp0700615"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1993.tb05886.x"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2013.2"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.619"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061825"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061523"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737429"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201644"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24552"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.09.015"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-440776"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-07-587824"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124256"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802361"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401720"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.06.009"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402425"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.11.017"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.3109\/08820139109026241"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916930310001602137"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18025"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3123"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.05.042"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20132620"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38061"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-230631"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20032000"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002821"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2008.07.009"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201646641","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201646641","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T09:27:55Z","timestamp":1695720475000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201646641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,31]]},"references-count":78,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1002\/eji.201646641"],"URL":"https:\/\/doi.org\/10.1002\/eji.201646641","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,31]]}}}