{"id":"https://openalex.org/W1581857504","doi":"https://doi.org/10.4049/jimmunol.173.5.2913","title":"Cutting Edge: TNFR-Associated Factor (TRAF) 6 Is Essential for MyD88-Dependent Pathway but Not Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-\u03b2 (TRIF)-Dependent Pathway in TLR Signaling","display_name":"Cutting Edge: TNFR-Associated Factor (TRAF) 6 Is Essential for MyD88-Dependent Pathway but Not Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-\u03b2 (TRIF)-Dependent Pathway in TLR Signaling","publication_year":2004,"publication_date":"2004-09-01","ids":{"openalex":"https://openalex.org/W1581857504","doi":"https://doi.org/10.4049/jimmunol.173.5.2913","mag":"1581857504","pmid":"https://pubmed.ncbi.nlm.nih.gov/15322147"},"language":"en","primary_location":{"id":"doi:10.4049/jimmunol.173.5.2913","doi":"https://doi.org/10.4049/jimmunol.173.5.2913","is_oa":false,"landing_page_url":"https://doi.org/10.4049/jimmunol.173.5.2913","pdf_url":null,"source":{"id":"https://openalex.org/S38008053","display_name":"The Journal of Immunology","issn_l":"0022-1767","issn":["0022-1767","1550-6606"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4320800377","host_organization_name":"American Association of Immunologists","host_organization_lineage":["https://openalex.org/P4320800377"],"host_organization_lineage_names":["American Association of Immunologists"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of Immunology","raw_type":"journal-article"},"parent_works":[],"lineage":["https://openalex.org/W1581857504"],"child_works_count":0,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5036792590","display_name":"Jin Gohda","orcid":"https://orcid.org/0000-0002-9929-9879","observed_orcids":["https://orcid.org/0000-0002-9929-9879"]},"institutions":[{"id":"https://openalex.org/I4405286826","display_name":"Institute of Medical Science, The University of Tokyo","ror":"https://ror.org/0376e0j29","country_code":"JP","type":"facility","lineage":["https://openalex.org/I4405286826","https://openalex.org/I74801974"]},{"id":"https://openalex.org/I74801974","display_name":"The University of Tokyo","ror":"https://ror.org/057zh3y96","country_code":"JP","type":"education","lineage":["https://openalex.org/I74801974"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Jin Gohda","raw_affiliation_strings":["Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo , Tokyo ,","*Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo , Tokyo ,","institution_ids":["https://openalex.org/I4405286826","https://openalex.org/I74801974"]},{"raw_affiliation_string":"*Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan;","institution_ids":["https://openalex.org/I4405286826","https://openalex.org/I74801974"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5064223580","display_name":"Takayuki Matsumura","orcid":"https://orcid.org/0000-0003-1760-3484","observed_orcids":["https://orcid.org/0000-0003-1760-3484"]},"institutions":[{"id":"https://openalex.org/I4405286826","display_name":"Institute of Medical Science, The University of Tokyo","ror":"https://ror.org/0376e0j29","country_code":"JP","type":"facility","lineage":["https://openalex.org/I4405286826","https://openalex.org/I74801974"]},{"id":"https://openalex.org/I74801974","display_name":"The University of Tokyo","ror":"https://ror.org/057zh3y96","country_code":"JP","type":"education","lineage":["https://openalex.org/I74801974"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Takayuki Matsumura","raw_affiliation_strings":["Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo , Tokyo ,","*Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo , Tokyo ,","institution_ids":["https://openalex.org/I4405286826","https://openalex.org/I74801974"]},{"raw_affiliation_string":"*Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan;","institution_ids":["https://openalex.org/I4405286826","https://openalex.org/I74801974"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5058632940","display_name":"Jun\u2010ichiro Inoue","orcid":"https://orcid.org/0000-0001-6389-7036","observed_orcids":["https://orcid.org/0000-0001-6389-7036"]},"institutions":[{"id":"https://openalex.org/I4405286826","display_name":"Institute of Medical Science, The University of Tokyo","ror":"https://ror.org/0376e0j29","country_code":"JP","type":"facility","lineage":["https://openalex.org/I4405286826","https://openalex.org/I74801974"]},{"id":"https://openalex.org/I74801974","display_name":"The University of Tokyo","ror":"https://ror.org/057zh3y96","country_code":"JP","type":"education","lineage":["https://openalex.org/I74801974"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Jun-ichiro Inoue","raw_affiliation_strings":["Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo , Tokyo ,","*Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo , Tokyo ,","institution_ids":["https://openalex.org/I4405286826","https://openalex.org/I74801974"]},{"raw_affiliation_string":"*Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan;","institution_ids":["https://openalex.org/I4405286826","https://openalex.org/I74801974"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":3500,"currency":"USD","value_usd":3500},"apc_paid":null,"fwci":7.822,"has_fulltext":false,"cited_by_count":319,"citation_normalized_percentile":{"value":0.98161237,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":97,"max":100},"biblio":{"volume":"173","issue":"5","first_page":"2913","last_page":"2917"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10371","display_name":"Immune Response and Inflammation","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10371","display_name":"Immune Response and Inflammation","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11591","display_name":"NF-\u03baB Signaling Pathways","score":0.0005000000237487257,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11078","display_name":"Inflammasome and immune disorders","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/traf6","display_name":"TRAF6","score":0.9990000128746033},{"id":"https://openalex.org/keywords/toll-like-receptor-signaling","display_name":"Toll-like receptor signaling","score":0.7559999823570251},{"id":"https://openalex.org/keywords/nf-kappab-activation","display_name":"NF-\u03baB activation","score":0.9359999895095825},{"id":"https://openalex.org/keywords/mapk-activation","display_name":"MAPK activation","score":0.9909999966621399},{"id":"https://openalex.org/keywords/inflammatory-cytokine-production","display_name":"inflammatory cytokine production","score":0.8109999895095825},{"id":"https://openalex.org/keywords/tlr4","display_name":"TLR4","score":0.8669999837875366},{"id":"https://openalex.org/keywords/tlr2","display_name":"TLR2","score":0.8640000224113464},{"id":"https://openalex.org/keywords/tlr5","display_name":"TLR5","score":0.984000027179718},{"id":"https://openalex.org/keywords/tlr7","display_name":"TLR7","score":0.9879999756813049},{"id":"https://openalex.org/keywords/tlr9","display_name":"TLR9","score":0.9950000047683716},{"id":"https://openalex.org/keywords/tlr3","display_name":"TLR3","score":0.9800000190734863},{"id":"https://openalex.org/keywords/macrophages","display_name":"macrophages","score":0.9390000104904175}],"concepts":[{"id":"https://openalex.org/C43929388","wikidata":"https://www.wikidata.org/wiki/Q4050587","display_name":"TRIF","level":5,"score":0.9356024861335754},{"id":"https://openalex.org/C2781236682","wikidata":"https://www.wikidata.org/wiki/Q410015","display_name":"TLR2","level":4,"score":0.7810337543487549},{"id":"https://openalex.org/C183786373","wikidata":"https://www.wikidata.org/wiki/Q5964993","display_name":"Signal transducing adaptor protein","level":3,"score":0.7477900981903076},{"id":"https://openalex.org/C2776070231","wikidata":"https://www.wikidata.org/wiki/Q14914098","display_name":"TLR4","level":3,"score":0.6686104536056519},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.666898787021637},{"id":"https://openalex.org/C2776709828","wikidata":"https://www.wikidata.org/wiki/Q408004","display_name":"Toll-like receptor","level":4,"score":0.6249846816062927},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.591002345085144},{"id":"https://openalex.org/C2778420691","wikidata":"https://www.wikidata.org/wiki/Q14866230","display_name":"TLR3","level":5,"score":0.5178787708282471},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.511435866355896},{"id":"https://openalex.org/C2779836521","wikidata":"https://www.wikidata.org/wiki/Q14914081","display_name":"TLR7","level":5,"score":0.45789533853530884},{"id":"https://openalex.org/C2778690821","wikidata":"https://www.wikidata.org/wiki/Q212354","display_name":"Cytokine","level":2,"score":0.42585238814353943},{"id":"https://openalex.org/C2779138994","wikidata":"https://www.wikidata.org/wiki/Q15332550","display_name":"TLR9","level":5,"score":0.4218474328517914},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.40008240938186646},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3433232307434082},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.25600847601890564},{"id":"https://openalex.org/C136449434","wikidata":"https://www.wikidata.org/wiki/Q428253","display_name":"Innate immune system","level":3,"score":0.22037094831466675},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0935964286327362},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.037780046463012695},{"id":"https://openalex.org/C190727270","wikidata":"https://www.wikidata.org/wiki/Q874745","display_name":"DNA methylation","level":4,"score":0.0},{"id":"https://openalex.org/C150194340","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Gene expression","level":3,"score":0.0}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000943","descriptor_name":"Antigens, Differentiation","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008264","descriptor_name":"Macrophages","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008562","descriptor_name":"Membrane Glycoproteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D008562","descriptor_name":"Membrane Glycoproteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011506","descriptor_name":"Proteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D011506","descriptor_name":"Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011956","descriptor_name":"Receptors, Cell Surface","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011971","descriptor_name":"Receptors, Immunologic","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":true},{"descriptor_ui":"D017472","descriptor_name":"Receptors, Interleukin-1","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D017472","descriptor_name":"Receptors, Interleukin-1","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D033942","descriptor_name":"Adaptor Proteins, Vesicular Transport","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D033942","descriptor_name":"Adaptor Proteins, Vesicular Transport","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D048029","descriptor_name":"TNF Receptor-Associated Factor 6","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D048868","descriptor_name":"Adaptor Proteins, Signal Transducing","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051193","descriptor_name":"Toll-Like Receptors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051195","descriptor_name":"Toll-Like Receptor 2","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051196","descriptor_name":"Toll-Like Receptor 3","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051197","descriptor_name":"Toll-Like Receptor 4","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051198","descriptor_name":"Toll-Like Receptor 5","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051199","descriptor_name":"Toll-Like Receptor 7","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051217","descriptor_name":"Toll-Like Receptor 9","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051379","descriptor_name":"Mice","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D053594","descriptor_name":"Myeloid Differentiation Factor 88","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.4049/jimmunol.173.5.2913","doi":"https://doi.org/10.4049/jimmunol.173.5.2913","is_oa":false,"landing_page_url":"https://doi.org/10.4049/jimmunol.173.5.2913","pdf_url":null,"source":{"id":"https://openalex.org/S38008053","display_name":"The Journal of Immunology","issn_l":"0022-1767","issn":["0022-1767","1550-6606"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4320800377","host_organization_name":"American Association of Immunologists","host_organization_lineage":["https://openalex.org/P4320800377"],"host_organization_lineage_names":["American Association of Immunologists"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of Immunology","raw_type":"journal-article"},{"id":"pmid:15322147","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/15322147","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of immunology (Baltimore, Md. : 1950)","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.504800021648407}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":23,"referenced_works":["https://openalex.org/W1967269498","https://openalex.org/W1981087308","https://openalex.org/W1982637996","https://openalex.org/W1989656760","https://openalex.org/W1995757311","https://openalex.org/W2013601771","https://openalex.org/W2032972084","https://openalex.org/W2037454778","https://openalex.org/W2049874360","https://openalex.org/W2051026238","https://openalex.org/W2064229941","https://openalex.org/W2064434771","https://openalex.org/W2068419165","https://openalex.org/W2076361525","https://openalex.org/W2098901296","https://openalex.org/W2108889221","https://openalex.org/W2120388636","https://openalex.org/W2124671153","https://openalex.org/W2130421043","https://openalex.org/W2145584783","https://openalex.org/W2148579227","https://openalex.org/W2155706758","https://openalex.org/W2160546595"],"related_works":["https://openalex.org/W1984616248","https://openalex.org/W2130421043","https://openalex.org/W1994392739","https://openalex.org/W2047172241","https://openalex.org/W2166303012","https://openalex.org/W112485854","https://openalex.org/W2153642560","https://openalex.org/W2155706758","https://openalex.org/W2118762274","https://openalex.org/W1989656760"],"abstract_inverted_index":{"Signaling":[0],"pathways":[1],"from":[2,45,56],"TLRs":[3,47],"are":[4],"mediated":[5],"by":[6],"the":[7,38,61,65],"Toll/IL-1R":[8],"(TIR)":[9],"domain-containing":[10,29,139],"adaptor":[11],"molecules.":[12],"TNF":[13],"receptor-associated":[14],"factor":[15],"(TRAF)":[16],"6":[17],"is":[18,128,134],"thought":[19],"to":[20,31,78],"activate":[21],"NF-kappaB":[22,82,101],"and":[23,59,75,83,98,102,110],"MAPKs":[24,84,103],"downstream":[25],"of":[26,34,41,67,81,87,100],"these":[27],"TIR":[28,138],"proteins":[30],"induce":[32,79],"production":[33,86,94],"inflammatory":[35,88],"cytokines.":[36],"However,":[37],"precise":[39],"role":[40],"TRAF6":[42,127],"in":[43,112],"signaling":[44,119,132],"individual":[46],"has":[48],"not":[49,121,135],"been":[50],"appropriately":[51],"addressed.":[52],"We":[53],"analyzed":[54],"macrophages":[55],"TRAF6-deficient":[57],"mice":[58],"made":[60],"following":[62],"observations.":[63],"In":[64],"absence":[66],"TRAF6,":[68],"1)":[69],"ligands":[70],"for":[71,130,137],"TLR2,":[72],"TLR5,":[73],"TLR7,":[74],"TLR9":[76],"failed":[77],"activation":[80,99],"or":[85],"cytokines;":[89],"2)":[90],"TLR4":[91],"ligand-induced":[92],"cytokine":[93],"was":[95,104,120],"remarkably":[96],"reduced":[97],"observed,":[105],"albeit":[106],"with":[107,114],"delayed":[108],"kinetics;":[109],"3)":[111],"contrast":[113],"previously":[115],"reported":[116],"findings,":[117],"TLR3":[118],"affected.":[122],"These":[123],"results":[124],"indicate":[125],"that":[126],"essential":[129],"MyD88-dependent":[131],"but":[133],"required":[136],"adaptor-inducing":[140],"IFN-beta":[141],"(TRIF)-dependent":[142],"signaling.":[143]},"counts_by_year":[{"year":2026,"cited_by_count":5},{"year":2025,"cited_by_count":11},{"year":2024,"cited_by_count":11},{"year":2023,"cited_by_count":11},{"year":2022,"cited_by_count":8},{"year":2021,"cited_by_count":16},{"year":2020,"cited_by_count":13},{"year":2019,"cited_by_count":16},{"year":2018,"cited_by_count":10},{"year":2017,"cited_by_count":14},{"year":2016,"cited_by_count":13},{"year":2015,"cited_by_count":9},{"year":2014,"cited_by_count":14},{"year":2013,"cited_by_count":15},{"year":2012,"cited_by_count":14}],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2016-06-24T00:00:00"}