CD82 controls CpG-dependent TLR9 signaling

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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-kappa B 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.
Publisher
FEDERATION AMER SOC EXP BIOL
Issue Date
2019-11
Language
English
Article Type
Article
Citation

FASEB JOURNAL, v.33, no.11, pp.12500 - 12514

ISSN
0892-6638
DOI
10.1096/fj.201901547R
URI
http://hdl.handle.net/10203/272213
Appears in Collection
MSE-Journal Papers(저널논문)
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