DOI: 10.4049/jimmunol.173.5.2913. Cutting Edge: TNFR-Associated Factor (TRAF) 6 Is Essential for MyD88-Dependent Pathway but Not Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-β (TRIF)-Dependent Pathway in TLR Signaling

Cutting Edge: TNFR-Associated Factor (TRAF) 6 Is Essential for MyD88-Dependent Pathway but Not Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-β (TRIF)-Dependent Pathway in TLR Signaling

10.4049/jimmunol.173.5.2913

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

Abstract Signaling pathways from TLRs are mediated by the Toll/IL-1R (TIR) domain-containing adaptor molecules. TNF receptor-associated factor (TRAF) 6 is thought to activate NF-κB and MAPKs downstream of these TIR domain-containing proteins to induce production of inflammatory cytokines. However, the precise role of TRAF6 in signaling from individual TLRs has not been appropriately addressed. We analyzed macrophages from TRAF6-deficient mice and made the following observations. In the absence of TRAF6, 1) ligands for TLR2, TLR5, TLR7, and TLR9 failed to induce activation of NF-κB and MAPKs or production of inflammatory cytokines; 2) TLR4 ligand-induced cytokine production was remarkably reduced and activation of NF-κB and MAPKs was observed, albeit with delayed kinetics; and 3) in contrast with previously reported findings, TLR3 signaling was not affected. These results indicate that TRAF6 is essential for MyD88-dependent signaling but is not required for TIR domain-containing adaptor-inducing IFN-β (TRIF)-dependent signaling.

Bibliography

Gohda, J., Matsumura, T., & Inoue, J. (2004). Cutting Edge: TNFR-Associated Factor (TRAF) 6 Is Essential for MyD88-Dependent Pathway but Not Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-Î² (TRIF)-Dependent Pathway in TLR Signaling. The Journal of Immunology, 173(5), 2913â2917.

Authors 3

Jin Gohda (first)
Takayuki Matsumura (additional)
Jun-ichiro Inoue (additional)

References 23 Referenced 243

{'first-page': '643', 'volume-title': 'Biochem. Soc. Trans.', 'year': '2003', 'key': '2025032617333347800_R1'} / Biochem. Soc. Trans. (2003)
{'first-page': '286', 'volume-title': 'Trends Immunol.', 'year': '2003', 'key': '2025032617333347800_R2'} / Trends Immunol. (2003)
{'first-page': '329', 'volume-title': 'Nature', 'year': '2002', 'key': '2025032617333347800_R3'} / Nature (2002)
{'first-page': '324', 'volume-title': 'Nature', 'year': '2002', 'key': '2025032617333347800_R4'} / Nature (2002)
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{'first-page': '743', 'volume-title': 'Nature', 'year': '2003', 'key': '2025032617333347800_R7'} / Nature (2003)
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Dates

Type	When
Created	11 years, 4 months ago (April 20, 2014, 8:03 p.m.)
Deposited	5 months ago (March 29, 2025, 1:44 p.m.)
Indexed	1 month, 1 week ago (July 22, 2025, 6:42 a.m.)
Issued	21 years ago (Sept. 1, 2004)
Published	21 years ago (Sept. 1, 2004)
Published Online	21 years ago (Sept. 1, 2004)
Published Print	21 years ago (Sept. 1, 2004)

Funders 0

None

BibTeX

@article{Gohda_2004, title={Cutting Edge: TNFR-Associated Factor (TRAF) 6 Is Essential for MyD88-Dependent Pathway but Not Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-β (TRIF)-Dependent Pathway in TLR Signaling}, volume={173}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.173.5.2913}, DOI={10.4049/jimmunol.173.5.2913}, number={5}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Gohda, Jin and Matsumura, Takayuki and Inoue, Jun-ichiro}, year={2004}, month=sep, pages={2913–2917} }

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  "abstract": "<jats:title>Abstract</jats:title>\n               <jats:p>Signaling pathways from TLRs are mediated by the Toll/IL-1R (TIR) domain-containing adaptor molecules. TNF receptor-associated factor (TRAF) 6 is thought to activate NF-\u03baB and MAPKs downstream of these TIR domain-containing proteins to induce production of inflammatory cytokines. However, the precise role of TRAF6 in signaling from individual TLRs has not been appropriately addressed. We analyzed macrophages from TRAF6-deficient mice and made the following observations. In the absence of TRAF6, 1) ligands for TLR2, TLR5, TLR7, and TLR9 failed to induce activation of NF-\u03baB and MAPKs or production of inflammatory cytokines; 2) TLR4 ligand-induced cytokine production was remarkably reduced and activation of NF-\u03baB and MAPKs was observed, albeit with delayed kinetics; and 3) in contrast with previously reported findings, TLR3 signaling was not affected. These results indicate that TRAF6 is essential for MyD88-dependent signaling but is not required for TIR domain-containing adaptor-inducing IFN-\u03b2 (TRIF)-dependent signaling.</jats:p>",
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