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000145064 0247_ $$2doi$$a10.1096/fj.201901547R
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000145064 037__ $$aDZNE-2020-00423
000145064 041__ $$aEnglish
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000145064 1001_ $$aKhan, Nida S$$b0
000145064 245__ $$aCD82 controls CpG-dependent TLR9 signaling.
000145064 260__ $$aHoboken, NJ$$bWiley$$c2019
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000145064 520__ $$aThe tetraspanin CD82 is a potent suppressor of tumor metastasis and regulates several processes including signal transduction, cell adhesion, motility, and aggregation. However, the mechanisms by which CD82 participates in innate immunity are unknown. We report that CD82 is a key regulator of TLR9 trafficking and signaling. TLR9 recognizes unmethylated cytosine-phosphate-guanine (CpG) motifs present in viral, bacterial, and fungal DNA. We demonstrate that TLR9 and CD82 associate in macrophages, which occurs in the endoplasmic reticulum (ER) and post-ER. Moreover, CD82 is essential for TLR9-dependent myddosome formation in response to CpG stimulation. Finally, CD82 modulates TLR9-dependent NF-κB nuclear translocation, which is critical for inflammatory cytokine production. To our knowledge, this is the first time a tetraspanin has been implicated as a key regulator of TLR signaling. Collectively, our study demonstrates that CD82 is a specific regulator of TLR9 signaling, which may be critical in cancer immunotherapy approaches and coordinating the innate immune response to pathogens.
000145064 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000145064 542__ $$2Crossref$$i2019-08-13$$uhttp://onlinelibrary.wiley.com/termsAndConditions#vor
000145064 542__ $$2Crossref$$i2019-08-13$$uhttp://doi.wiley.com/10.1002/tdm_license_1.1
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000145064 650_7 $$2NLM Chemicals$$aCPG-oligonucleotide
000145064 650_7 $$2NLM Chemicals$$aCd82 antigen, mouse
000145064 650_7 $$2NLM Chemicals$$aCytokines
000145064 650_7 $$2NLM Chemicals$$aKangai-1 Protein
000145064 650_7 $$2NLM Chemicals$$aNF-kappa B
000145064 650_7 $$2NLM Chemicals$$aOligodeoxyribonucleotides
000145064 650_7 $$2NLM Chemicals$$aTlr9 protein, mouse
000145064 650_7 $$2NLM Chemicals$$aToll-Like Receptor 9
000145064 650_2 $$2MeSH$$aActive Transport, Cell Nucleus: drug effects
000145064 650_2 $$2MeSH$$aActive Transport, Cell Nucleus: genetics
000145064 650_2 $$2MeSH$$aActive Transport, Cell Nucleus: immunology
000145064 650_2 $$2MeSH$$aAnimals
000145064 650_2 $$2MeSH$$aCell Nucleus: genetics
000145064 650_2 $$2MeSH$$aCell Nucleus: immunology
000145064 650_2 $$2MeSH$$aCytokines: genetics
000145064 650_2 $$2MeSH$$aCytokines: immunology
000145064 650_2 $$2MeSH$$aEndoplasmic Reticulum: genetics
000145064 650_2 $$2MeSH$$aEndoplasmic Reticulum: immunology
000145064 650_2 $$2MeSH$$aEndoplasmic Reticulum: pathology
000145064 650_2 $$2MeSH$$aInflammation: genetics
000145064 650_2 $$2MeSH$$aInflammation: immunology
000145064 650_2 $$2MeSH$$aInflammation: pathology
000145064 650_2 $$2MeSH$$aKangai-1 Protein: genetics
000145064 650_2 $$2MeSH$$aKangai-1 Protein: immunology
000145064 650_2 $$2MeSH$$aMacrophages: immunology
000145064 650_2 $$2MeSH$$aMacrophages: pathology
000145064 650_2 $$2MeSH$$aMice
000145064 650_2 $$2MeSH$$aMice, Knockout
000145064 650_2 $$2MeSH$$aNF-kappa B: genetics
000145064 650_2 $$2MeSH$$aNF-kappa B: immunology
000145064 650_2 $$2MeSH$$aOligodeoxyribonucleotides: pharmacology
000145064 650_2 $$2MeSH$$aRAW 264.7 Cells
000145064 650_2 $$2MeSH$$aSignal Transduction: drug effects
000145064 650_2 $$2MeSH$$aSignal Transduction: genetics
000145064 650_2 $$2MeSH$$aSignal Transduction: immunology
000145064 650_2 $$2MeSH$$aToll-Like Receptor 9: genetics
000145064 650_2 $$2MeSH$$aToll-Like Receptor 9: immunology
000145064 7001_ $$aLukason, Daniel P$$b1
000145064 7001_ $$aFeliu, Marianela$$b2
000145064 7001_ $$aWard, Rebecca A$$b3
000145064 7001_ $$aLord, Allison K$$b4
000145064 7001_ $$aReedy, Jennifer L$$b5
000145064 7001_ $$aRamirez-Ortiz, Zaida G$$b6
000145064 7001_ $$aTam, Jenny M$$b7
000145064 7001_ $$aKasperkovitz, Pia V$$b8
000145064 7001_ $$aNegoro, Paige E$$b9
000145064 7001_ $$aVyas, Tammy D$$b10
000145064 7001_ $$aXu, Shuying$$b11
000145064 7001_ $$aBrinkmann, Melanie M$$b12
000145064 7001_ $$aAcharaya, Mridu$$b13
000145064 7001_ $$aArtavanis-Tsakonas, Katerina$$b14
000145064 7001_ $$aFrickel, Eva-Maria$$b15
000145064 7001_ $$aBecker, Christine E$$b16
000145064 7001_ $$aDagher, Zeina$$b17
000145064 7001_ $$0P:(DE-HGF)0$$aKim, You-Me$$b18
000145064 7001_ $$0P:(DE-2719)2000062$$aLatz, Eicke$$b19
000145064 7001_ $$aPloegh, Hidde L$$b20
000145064 7001_ $$aMansour, Michael K$$b21
000145064 7001_ $$aMiranti, Cindy K$$b22
000145064 7001_ $$aLevitz, Stuart M$$b23
000145064 7001_ $$0P:(DE-HGF)0$$aVyas, Jatin M$$b24$$eCorresponding author
000145064 77318 $$2Crossref$$3journal-article$$a10.1096/fj.201901547r$$b : Wiley, 2019-08-13$$n11$$p12500-12514$$tThe FASEB Journal$$v33$$x0892-6638$$y2019
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