SCIMP is a transmembrane non-TIR TLR adaptor that promotes proinflammatory cytokine production from macrophages

Luo, Lin, Bokil, Nilesh J., Wall, Adam A., Kapetanovic, Ronan, Lansdaal, Natalie M., Marceline, Faustine, Burgess, Belinda J., Tong, Samuel J., Guo, Zhong, Alexandrov, Kirill, Ross, Ian L., Hibbs, Margaret L., Stow, Jennifer L. and Sweet, Matthew J. (2017) SCIMP is a transmembrane non-TIR TLR adaptor that promotes proinflammatory cytokine production from macrophages. Nature Communications, 8 14133. doi:10.1038/ncomms14133


Author Luo, Lin
Bokil, Nilesh J.
Wall, Adam A.
Kapetanovic, Ronan
Lansdaal, Natalie M.
Marceline, Faustine
Burgess, Belinda J.
Tong, Samuel J.
Guo, Zhong
Alexandrov, Kirill
Ross, Ian L.
Hibbs, Margaret L.
Stow, Jennifer L.
Sweet, Matthew J.
Title SCIMP is a transmembrane non-TIR TLR adaptor that promotes proinflammatory cytokine production from macrophages
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2017-01-18
Year available 2017
Sub-type Article (original research)
DOI 10.1038/ncomms14133
Open Access Status DOI
Volume 8
Start page 14133
Total pages 14
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1600 Chemistry
1300 Biochemistry, Genetics and Molecular Biology
3100 Physics and Astronomy
Abstract Danger signals activate Toll-like receptors (TLRs), thereby initiating inflammatory responses. Canonical TLR signalling, via Toll/Interleukin-1 receptor domain (TIR)-containing adaptors and proinflammatory transcription factors such as NF-? B, occurs in many cell types; however, additional mechanisms are required for specificity of inflammatory responses in innate immune cells. Here we show that SCIMP, an immune-restricted, transmembrane adaptor protein (TRAP), promotes selective proinflammatory cytokine responses by direct modulation of TLR4. SCIMP is a non-TIR-containing adaptor, binding directly to the TLR4-TIR domain in response to lipopolysaccharide. In macrophages, SCIMP is constitutively associated with the Lyn tyrosine kinase, is required for tyrosine phosphorylation of TLR4, and facilitates TLR-inducible production of the proinflammatory cytokines IL-6 and IL-12p40. Point mutations in SCIMP abrogating TLR4 binding also prevent SCIMP-mediated cytokine production. SCIMP is, therefore, an immune-specific TLR adaptor that shapes host defence and inflammation.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID DP130101431
606788
APP1101072
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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