CD82 controls CpG-dependent TLR9 signaling.
Active Transport, Cell Nucleus
/ drug effects
Animals
Cell Nucleus
/ genetics
Cytokines
/ genetics
Endoplasmic Reticulum
/ genetics
Inflammation
/ genetics
Kangai-1 Protein
/ genetics
Macrophages
/ immunology
Mice
Mice, Knockout
NF-kappa B
/ genetics
Oligodeoxyribonucleotides
/ pharmacology
RAW 264.7 Cells
Signal Transduction
/ drug effects
Toll-Like Receptor 9
/ genetics
TLRs
macrophages
myddosome
tetraspanins
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
pubmed:
14
8
2019
medline:
27
5
2020
entrez:
14
8
2019
Statut:
ppublish
Résumé
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.-Khan, N. S., Lukason, D. P., Feliu, M., Ward, R. A., Lord, A. K., Reedy, J. L., Ramirez-Ortiz, Z. G., Tam, J. M., Kasperkovitz, P. V., Negoro, P. E., Vyas, T. D., Xu, S., Brinkmann, M. M., Acharaya, M., Artavanis-Tsakonas, K., Frickel, E.-M., Becker, C. E., Dagher, Z., Kim, Y.-M., Latz, E., Ploegh, H. L., Mansour, M. K., Miranti, C. K., Levitz, S. M., Vyas, J. M. CD82 controls CpG-dependent TLR9 signaling.
Identifiants
pubmed: 31408613
doi: 10.1096/fj.201901547R
pmc: PMC6988855
doi:
Substances chimiques
CPG-oligonucleotide
0
Cd82 antigen, mouse
0
Cytokines
0
Kangai-1 Protein
0
NF-kappa B
0
Oligodeoxyribonucleotides
0
Tlr9 protein, mouse
0
Toll-Like Receptor 9
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12500-12514Subventions
Organisme : NIAID NIH HHS
ID : R01 AI139615
Pays : United States
Organisme : Cancer Research UK
ID : FC001076
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_1202/12
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI097519
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI025780
Pays : United States
Organisme : Medical Research Council
ID : FC001076
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : FC001076
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI132638
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI092084
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI136529
Pays : United States
Organisme : Wellcome Trust
ID : FC001076
Pays : United Kingdom
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