{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T18:15:45Z","timestamp":1770488145399,"version":"3.49.0"},"reference-count":77,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,12,18]],"date-time":"2016-12-18T00:00:00Z","timestamp":1482019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000882","name":"University of Aberdeen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000882","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Exposure of bone\u2010marrow\u2010derived dendritic cells (<jats:styled-content style=\"fixed-case\">BMDC<\/jats:styled-content>) to high\u2010dose ultrapure lipopolysaccharide for 24 hr (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010primed <jats:styled-content style=\"fixed-case\">BMDC<\/jats:styled-content>) enhances their potency in preventing inter\u2010photoreceptor retinoid binding protein: complete Freund's adjuvant\u2010induced experimental autoimmune uveoretinitis (EAU). <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010primed <jats:styled-content style=\"fixed-case\">BMDC<\/jats:styled-content> are refractory to further exposure to <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> (= endotoxin tolerance), evidenced here by decreased phosphorylation of <jats:styled-content style=\"fixed-case\">TANK<\/jats:styled-content>\u2010binding kinase 1, interferon regulatory factor 3 (<jats:styled-content style=\"fixed-case\">IRF<\/jats:styled-content>3), c\u2010Jun N\u2010terminal kinase and p38 mitogen\u2010activated protein kinase as well as impaired nuclear translocation of nuclear factor <jats:italic>\u03ba<\/jats:italic>B (<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B) and <jats:styled-content style=\"fixed-case\">IRF<\/jats:styled-content>3, resulting in reduced tumour necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic> (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010<jats:italic>\u03b1<\/jats:italic>), interleukin\u20106 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106), <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201012 and interferon\u2010<jats:italic>\u03b2<\/jats:italic> secretion. <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010primed <jats:styled-content style=\"fixed-case\">BMDC<\/jats:styled-content> also show reduced surface expression of Toll\u2010like receptor\u20104 and up\u2010regulation of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>14, followed by increased apoptosis, mediated via nuclear factor of activated T cells (<jats:styled-content style=\"fixed-case\">NFAT<\/jats:styled-content>c)\u20102 signalling. <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010primed <jats:styled-content style=\"fixed-case\">BMDC<\/jats:styled-content> are not only homotolerant to <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> but are heterotolerant to alternative pathogen\u2010associated molecular pattern ligands, such as mycobacterial protein extract (<jats:italic>Mycobacterium tuberculosis<\/jats:italic>). Specifically, while <jats:italic>M. tuberculosis<\/jats:italic> protein extract induces secretion of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic>,<jats:styled-content style=\"fixed-case\"> TNF<\/jats:styled-content>\u2010<jats:italic>\u03b1<\/jats:italic> and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 in unprimed <jats:styled-content style=\"fixed-case\">BMDC<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> LPS<\/jats:styled-content>\u2010primed <jats:styled-content style=\"fixed-case\">BMDC<\/jats:styled-content> fail to secrete these cytokines in response to <jats:italic>M. tuberculosis<\/jats:italic>. We propose that <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> priming of <jats:styled-content style=\"fixed-case\">BMDC<\/jats:styled-content>, by exposure to high doses of <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> for 24 hr, stabilizes their tolerogenicity rather than promoting immunogenicity, and does so by multiple mechanisms, namely (i) generation of tolerogenic apoptotic <jats:styled-content style=\"fixed-case\">BMDC<\/jats:styled-content> through <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>14:<jats:styled-content style=\"fixed-case\">NFAT<\/jats:styled-content>c signalling; (ii) reduction of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B and <jats:styled-content style=\"fixed-case\">IRF<\/jats:styled-content>3 signalling and downstream pro\u2010inflammatory cytokine production; and (iii) blockade of inflammasome activation.<\/jats:p>","DOI":"10.1111\/imm.12691","type":"journal-article","created":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T18:44:23Z","timestamp":1479321863000},"page":"364-377","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Lipopolysaccharide\u2010primed heterotolerant dendritic cells suppress experimental autoimmune uveoretinitis by multiple mechanisms"],"prefix":"10.1111","volume":"150","author":[{"given":"Izabela P.","family":"Klaska","sequence":"first","affiliation":[{"name":"Institute of Ophthalmology University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Muckersie","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences University of Aberdeen Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Martin\u2010Granados","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences University of Aberdeen Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Christofi","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences University of Aberdeen Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John V.","family":"Forrester","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences University of Aberdeen Aberdeen UK"},{"name":"Lions Eye Institute University of Western Australia Perth WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,12,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2003.037226"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01675857"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42440"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.81.12.1107"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICU.0b013e3282f03d42"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/09273940903072443"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2013.02.002"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0307166"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00182-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.06.001"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.231606698"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.08.015"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa9301"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102015\u2010208456"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.6.3889"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2009.34"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807185105"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141040"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-012-8293-7"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737400"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1845"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00198"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0608374"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt.10.56"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-10-3991"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2011.01.034"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052456"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4234"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2014.09.017"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2010.05.026"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.471"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12440"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1179\/096805104225003997"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(02)01613-1"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2011.06.020"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(99)00037-3"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.1.508"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxf046"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.11.5564"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0309189"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2011.12.002"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-006-0356-9"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753425910393540"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.2.618"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939782"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-017368"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08118"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502355"},{"key":"e_1_2_9_50_1","first-page":"30011","article-title":"Murine pattern recognition receptor dectin\u20101 is essential in the development of experimental autoimmune uveoretinitis","volume":"26","author":"Stoppelkamp S","year":"2015","journal-title":"Mol Immunol"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502080"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2008.06.012"},{"key":"e_1_2_9_53_1","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.4049\/jimmunol.140.5.1490","article-title":"A new model of autoimmune disease. Experimental autoimmune uveoretinitis induced in mice with two different retinal antigens.","volume":"140","author":"Caspi RR","year":"1988","journal-title":"J Immunol"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.10.6173"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900824"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-869-0_22"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.07.009"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxf089"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/405310"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2014.06.041"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2011.10.001"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343800"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-101011-155745"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2012.03.006"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0812401"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.2002.01115.x"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-003-0521-0"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.103259"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27756"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12038"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.126383"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.05.018"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjv032"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2013.51"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2446"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.7.3476"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2004.12.003"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.09.051"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fimm.12691","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.12691","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T23:00:16Z","timestamp":1695510016000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.12691"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,18]]},"references-count":77,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["10.1111\/imm.12691"],"URL":"https:\/\/doi.org\/10.1111\/imm.12691","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,18]]},"assertion":[{"value":"2016-06-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-11-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}