001     145064
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024 7 _ |a 10.1096/fj.201901547R
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024 7 _ |a pmid:31408613
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024 7 _ |a pmc:PMC6988855
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024 7 _ |a 0892-6638
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024 7 _ |a 1530-6860
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037 _ _ |a DZNE-2020-00423
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Khan, Nida S
|b 0
245 _ _ |a CD82 controls CpG-dependent TLR9 signaling.
260 _ _ |a Hoboken, NJ
|c 2019
|b Wiley
264 _ 1 |3 online
|2 Crossref
|b Wiley
|c 2019-08-13
264 _ 1 |3 print
|2 Crossref
|b Wiley
|c 2019-11-01
336 7 _ |a article
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336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
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542 _ _ |i 2019-08-13
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|u http://onlinelibrary.wiley.com/termsAndConditions#vor
542 _ _ |i 2019-08-13
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|u http://doi.wiley.com/10.1002/tdm_license_1.1
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650 _ 7 |a CPG-oligonucleotide
|2 NLM Chemicals
650 _ 7 |a Cd82 antigen, mouse
|2 NLM Chemicals
650 _ 7 |a Cytokines
|2 NLM Chemicals
650 _ 7 |a Kangai-1 Protein
|2 NLM Chemicals
650 _ 7 |a NF-kappa B
|2 NLM Chemicals
650 _ 7 |a Oligodeoxyribonucleotides
|2 NLM Chemicals
650 _ 7 |a Tlr9 protein, mouse
|2 NLM Chemicals
650 _ 7 |a Toll-Like Receptor 9
|2 NLM Chemicals
650 _ 2 |a Active Transport, Cell Nucleus: drug effects
|2 MeSH
650 _ 2 |a Active Transport, Cell Nucleus: genetics
|2 MeSH
650 _ 2 |a Active Transport, Cell Nucleus: immunology
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Cell Nucleus: genetics
|2 MeSH
650 _ 2 |a Cell Nucleus: immunology
|2 MeSH
650 _ 2 |a Cytokines: genetics
|2 MeSH
650 _ 2 |a Cytokines: immunology
|2 MeSH
650 _ 2 |a Endoplasmic Reticulum: genetics
|2 MeSH
650 _ 2 |a Endoplasmic Reticulum: immunology
|2 MeSH
650 _ 2 |a Endoplasmic Reticulum: pathology
|2 MeSH
650 _ 2 |a Inflammation: genetics
|2 MeSH
650 _ 2 |a Inflammation: immunology
|2 MeSH
650 _ 2 |a Inflammation: pathology
|2 MeSH
650 _ 2 |a Kangai-1 Protein: genetics
|2 MeSH
650 _ 2 |a Kangai-1 Protein: immunology
|2 MeSH
650 _ 2 |a Macrophages: immunology
|2 MeSH
650 _ 2 |a Macrophages: pathology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a NF-kappa B: genetics
|2 MeSH
650 _ 2 |a NF-kappa B: immunology
|2 MeSH
650 _ 2 |a Oligodeoxyribonucleotides: pharmacology
|2 MeSH
650 _ 2 |a RAW 264.7 Cells
|2 MeSH
650 _ 2 |a Signal Transduction: drug effects
|2 MeSH
650 _ 2 |a Signal Transduction: genetics
|2 MeSH
650 _ 2 |a Signal Transduction: immunology
|2 MeSH
650 _ 2 |a Toll-Like Receptor 9: genetics
|2 MeSH
650 _ 2 |a Toll-Like Receptor 9: immunology
|2 MeSH
700 1 _ |a Lukason, Daniel P
|b 1
700 1 _ |a Feliu, Marianela
|b 2
700 1 _ |a Ward, Rebecca A
|b 3
700 1 _ |a Lord, Allison K
|b 4
700 1 _ |a Reedy, Jennifer L
|b 5
700 1 _ |a Ramirez-Ortiz, Zaida G
|b 6
700 1 _ |a Tam, Jenny M
|b 7
700 1 _ |a Kasperkovitz, Pia V
|b 8
700 1 _ |a Negoro, Paige E
|b 9
700 1 _ |a Vyas, Tammy D
|b 10
700 1 _ |a Xu, Shuying
|b 11
700 1 _ |a Brinkmann, Melanie M
|b 12
700 1 _ |a Acharaya, Mridu
|b 13
700 1 _ |a Artavanis-Tsakonas, Katerina
|b 14
700 1 _ |a Frickel, Eva-Maria
|b 15
700 1 _ |a Becker, Christine E
|b 16
700 1 _ |a Dagher, Zeina
|b 17
700 1 _ |a Kim, You-Me
|0 P:(DE-HGF)0
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700 1 _ |a Latz, Eicke
|0 P:(DE-2719)2000062
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700 1 _ |a Ploegh, Hidde L
|b 20
700 1 _ |a Mansour, Michael K
|b 21
700 1 _ |a Miranti, Cindy K
|b 22
700 1 _ |a Levitz, Stuart M
|b 23
700 1 _ |a Vyas, Jatin M
|0 P:(DE-HGF)0
|b 24
|e Corresponding author
773 1 8 |a 10.1096/fj.201901547r
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LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21