% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Khan:145064, author = {Khan, Nida S and Lukason, Daniel P and Feliu, Marianela and Ward, Rebecca A and Lord, Allison K and Reedy, Jennifer L and Ramirez-Ortiz, Zaida G and Tam, Jenny M and Kasperkovitz, Pia V and Negoro, Paige E and Vyas, Tammy D and Xu, Shuying and Brinkmann, Melanie M and Acharaya, Mridu and Artavanis-Tsakonas, Katerina and Frickel, Eva-Maria and Becker, Christine E and Dagher, Zeina and Kim, You-Me and Latz, Eicke and Ploegh, Hidde L and Mansour, Michael K and Miranti, Cindy K and Levitz, Stuart M and Vyas, Jatin M}, title = {{CD}82 controls {C}p{G}-dependent {TLR}9 signaling.}, journal = {The FASEB journal}, volume = {33}, number = {11}, issn = {0892-6638}, address = {Hoboken, NJ}, publisher = {Wiley}, reportid = {DZNE-2020-00423}, pages = {12500-12514}, year = {2019}, abstract = {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.}, keywords = {Active Transport, Cell Nucleus: drug effects / Active Transport, Cell Nucleus: genetics / Active Transport, Cell Nucleus: immunology / Animals / Cell Nucleus: genetics / Cell Nucleus: immunology / Cytokines: genetics / Cytokines: immunology / Endoplasmic Reticulum: genetics / Endoplasmic Reticulum: immunology / Endoplasmic Reticulum: pathology / Inflammation: genetics / Inflammation: immunology / Inflammation: pathology / Kangai-1 Protein: genetics / Kangai-1 Protein: immunology / Macrophages: immunology / Macrophages: pathology / Mice / Mice, Knockout / NF-kappa B: genetics / NF-kappa B: immunology / Oligodeoxyribonucleotides: pharmacology / RAW 264.7 Cells / Signal Transduction: drug effects / Signal Transduction: genetics / Signal Transduction: immunology / Toll-Like Receptor 9: genetics / Toll-Like Receptor 9: immunology / 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)}, cin = {Bonn common / AG Latz}, ddc = {570}, cid = {I:(DE-2719)6000011 / I:(DE-2719)1013024}, pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)}, pid = {G:(DE-HGF)POF3-342}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:31408613}, pmc = {pmc:PMC6988855}, doi = {10.1096/fj.201901547R}, url = {https://pub.dzne.de/record/145064}, }