145064 20250415100044.0 10.1096/fj.201901547R doi pmid:31408613 pmid pmc:PMC6988855 pmc 0892-6638 ISSN 1530-6860 ISSN altmetric:64959782 altmetric DZNE-2020-00423 English 570 Khan, Nida S 0 CD82 controls CpG-dependent TLR9 signaling. Hoboken, NJ 2019 Wiley online Crossref Wiley 2019-08-13 print Crossref Wiley 2019-11-01 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1744701697_3428 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote The tetraspanin CD82 is a potent suppressor of tumor metastasis and regulates several processes including signal transduction, cell adhesion, motility, and aggregation. However, the mechanisms by which CD82 participates in innate immunity are unknown. We report that CD82 is a key regulator of TLR9 trafficking and signaling. TLR9 recognizes unmethylated cytosine-phosphate-guanine (CpG) motifs present in viral, bacterial, and fungal DNA. We demonstrate that TLR9 and CD82 associate in macrophages, which occurs in the endoplasmic reticulum (ER) and post-ER. Moreover, CD82 is essential for TLR9-dependent myddosome formation in response to CpG stimulation. Finally, CD82 modulates TLR9-dependent NF-κB nuclear translocation, which is critical for inflammatory cytokine production. To our knowledge, this is the first time a tetraspanin has been implicated as a key regulator of TLR signaling. Collectively, our study demonstrates that CD82 is a specific regulator of TLR9 signaling, which may be critical in cancer immunotherapy approaches and coordinating the innate immune response to pathogens. 342 - Disease Mechanisms and Model Systems (POF3-342) G:(DE-HGF)POF3-342 POF3-342 POF III 0 2019-08-13 Crossref http://onlinelibrary.wiley.com/termsAndConditions#vor 2019-08-13 Crossref http://doi.wiley.com/10.1002/tdm_license_1.1 Dataset connected to CrossRef, PubMed, CPG-oligonucleotide NLM Chemicals Cd82 antigen, mouse NLM Chemicals Cytokines NLM Chemicals Kangai-1 Protein NLM Chemicals NF-kappa B NLM Chemicals Oligodeoxyribonucleotides NLM Chemicals Tlr9 protein, mouse NLM Chemicals Toll-Like Receptor 9 NLM Chemicals Active Transport, Cell Nucleus: drug effects MeSH Active Transport, Cell Nucleus: genetics MeSH Active Transport, Cell Nucleus: immunology MeSH Animals MeSH Cell Nucleus: genetics MeSH Cell Nucleus: immunology MeSH Cytokines: genetics MeSH Cytokines: immunology MeSH Endoplasmic Reticulum: genetics MeSH Endoplasmic Reticulum: immunology MeSH Endoplasmic Reticulum: pathology MeSH Inflammation: genetics MeSH Inflammation: immunology MeSH Inflammation: pathology MeSH Kangai-1 Protein: genetics MeSH Kangai-1 Protein: immunology MeSH Macrophages: immunology MeSH Macrophages: pathology MeSH Mice MeSH Mice, Knockout MeSH NF-kappa B: genetics MeSH NF-kappa B: immunology MeSH Oligodeoxyribonucleotides: pharmacology MeSH RAW 264.7 Cells MeSH Signal Transduction: drug effects MeSH Signal Transduction: genetics MeSH Signal Transduction: immunology MeSH Toll-Like Receptor 9: genetics MeSH Toll-Like Receptor 9: immunology MeSH Lukason, Daniel P 1 Feliu, Marianela 2 Ward, Rebecca A 3 Lord, Allison K 4 Reedy, Jennifer L 5 Ramirez-Ortiz, Zaida G 6 Tam, Jenny M 7 Kasperkovitz, Pia V 8 Negoro, Paige E 9 Vyas, Tammy D 10 Xu, Shuying 11 Brinkmann, Melanie M 12 Acharaya, Mridu 13 Artavanis-Tsakonas, Katerina 14 Frickel, Eva-Maria 15 Becker, Christine E 16 Dagher, Zeina 17 Kim, You-Me P:(DE-HGF)0 18 Latz, Eicke P:(DE-2719)2000062 19 Ploegh, Hidde L 20 Mansour, Michael K 21 Miranti, Cindy K 22 Levitz, Stuart M 23 Vyas, Jatin M P:(DE-HGF)0 24 Corresponding author 10.1096/fj.201901547r : Wiley, 2019-08-13 11 12500-12514 journal-article Crossref The FASEB Journal 33 2019 0892-6638 10.1096/fj.201901547R Vol. 33, no. 11, p. 12500 - 12514 PERI:(DE-600)1468876-1 11 12500-12514 The FASEB journal 33 2019 0892-6638 OpenAccess http://pub.dzne.de/record/145064/files/DZNE-2020-00423.pdf OpenAccess pdfa http://pub.dzne.de/record/145064/files/DZNE-2020-00423.pdf?subformat=pdfa oai:pub.dzne.de:145064 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 19 P:(DE-2719)2000062 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-342 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Disease Mechanisms and Model Systems 0 2019 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-08 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-08 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-08 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2020-02-27 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2022-11-08 JCR StatID:(DE-HGF)0100 StatID FASEB J : 2021 2022-11-08 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-08 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2022-11-08 OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID ASC 2022-11-08 IF >= 5 StatID:(DE-HGF)9905 StatID FASEB J : 2021 2022-11-08 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2020-02-27 Creative Commons Attribution CC BY 4.0 LIC:(DE-HGF)CCBY4 HGFVOC DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-08 I:(DE-2719)6000011 Bonn common Bonn common 0 I:(DE-2719)1013024 AG Latz Innate Immunity in Neurodegeneration 1 journal VDB UNRESTRICTED I:(DE-2719)6000011 I:(DE-2719)1013024 FullTexts -- missing cx lookup -- 10.1038/nrm1736 Crossref 10.1038/nrm1736 -- missing cx lookup -- 10.1016/j.micinf.2009.11.001 Crossref 10.1016/j.micinf.2009.11.001 -- missing cx lookup -- 10.1038/nrc3640 Crossref 10.1038/nrc3640 -- missing cx lookup -- 10.3389/fimmu.2015.00653 Crossref 10.3389/fimmu.2015.00653 -- missing cx lookup -- 10.1016/j.tcb.2009.06.004 Crossref 10.1016/j.tcb.2009.06.004 -- missing cx lookup -- 10.1016/j.cellsig.2015.07.004 Crossref 10.1016/j.cellsig.2015.07.004 -- missing cx lookup -- 10.1016/j.stem.2016.01.013 Crossref 10.1016/j.stem.2016.01.013 -- missing cx lookup -- 10.1038/onc.2015.449 Crossref 10.1038/onc.2015.449 -- missing cx lookup -- 10.1016/j.yexcr.2015.11.006 Crossref 10.1016/j.yexcr.2015.11.006 -- missing cx lookup -- 10.1016/j.molmed.2005.10.002 Crossref 10.1016/j.molmed.2005.10.002 -- missing cx lookup -- 10.1016/j.febslet.2011.08.031 Crossref 10.1016/j.febslet.2011.08.031 -- missing cx lookup -- 10.1038/nrd2659 Crossref 10.1038/nrd2659 -- missing cx lookup -- 10.1038/ni750 Crossref 10.1038/ni750 -- missing cx lookup -- 10.4049/jimmunol.178.11.7199 Crossref 10.4049/jimmunol.178.11.7199 -- missing cx lookup -- 10.1128/IAI.01135-10 Crossref 10.1128/IAI.01135-10 1998 Crossref Hammond C. 1998 -- missing cx lookup -- 10.4049/jimmunol.1500357 Crossref 10.4049/jimmunol.1500357 -- missing cx lookup -- 10.1038/nri2587 Crossref 10.1038/nri2587 -- missing cx lookup -- 10.1038/ni.1863 Crossref 10.1038/ni.1863 -- missing cx lookup -- 10.1038/ni1479 Crossref 10.1038/ni1479 -- missing cx lookup -- 10.1074/jbc.M109.022392 Crossref 10.1074/jbc.M109.022392 -- missing cx lookup -- 10.1016/j.cell.2014.01.019 Crossref 10.1016/j.cell.2014.01.019 -- missing cx lookup -- 10.1038/nature09121 Crossref 10.1038/nature09121 -- missing cx lookup -- 10.1083/jcb.200612056 Crossref 10.1083/jcb.200612056 -- missing cx lookup -- 10.1038/nature06726 Crossref 10.1038/nature06726 -- missing cx lookup -- 10.1126/science.1187029 Crossref 10.1126/science.1187029 -- missing cx lookup -- 10.1182/blood-2008-12-192344 Crossref 10.1182/blood-2008-12-192344 -- missing cx lookup -- 10.1038/nature07405 Crossref 10.1038/nature07405 -- missing cx lookup -- 10.1038/ni.1669 Crossref 10.1038/ni.1669 -- missing cx lookup -- 10.4049/jimmunol.1202342 Crossref 10.4049/jimmunol.1202342 -- missing cx lookup -- 10.1038/35047123 Crossref 10.1038/35047123 -- missing cx lookup -- 10.1038/ni1028 Crossref 10.1038/ni1028 -- missing cx lookup -- 10.4049/jimmunol.1401545 Crossref 10.4049/jimmunol.1401545 -- missing cx lookup -- 10.4049/jimmunol.1801384 Crossref 10.4049/jimmunol.1801384 -- missing cx lookup -- 10.1038/ni.3711 Crossref 10.1038/ni.3711 -- missing cx lookup -- 10.4049/jimmunol.1002760 Crossref 10.4049/jimmunol.1002760 -- missing cx lookup -- 10.1038/ni.1636 Crossref 10.1038/ni.1636 -- missing cx lookup -- 10.1073/pnas.1518976113 Crossref 10.1073/pnas.1518976113 -- missing cx lookup -- 10.1016/S0306-3623(97)00434-5 Crossref 10.1016/S0306-3623(97)00434-5 -- missing cx lookup -- 10.1038/srep44042 Crossref 10.1038/srep44042 -- missing cx lookup -- 10.3389/fimmu.2018.01491 Crossref 10.3389/fimmu.2018.01491 -- missing cx lookup -- 10.1242/jcs.088047 Crossref 10.1242/jcs.088047 -- missing cx lookup -- 10.1016/j.molmed.2007.09.002 Crossref 10.1016/j.molmed.2007.09.002 -- missing cx lookup -- 10.1038/nri1548 Crossref 10.1038/nri1548 -- missing cx lookup -- 10.4049/jimmunol.0802797 Crossref 10.4049/jimmunol.0802797 -- missing cx lookup -- 10.1002/eji.1830270712 Crossref 10.1002/eji.1830270712 -- missing cx lookup -- 10.1074/jbc.M601337200 Crossref 10.1074/jbc.M601337200 -- missing cx lookup -- 10.4049/jimmunol.178.1.154 Crossref 10.4049/jimmunol.178.1.154 2018 Crossref Koh H. 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