The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer
Open accessAbstract
In atherosclerosis and Alzheimer's disease, deposition of the altered self components oxidized low-density lipoprotein (LDL) and amyloid-beta triggers a protracted sterile inflammatory response. Although chronic stimulation of the innate immune system is believed to underlie the pathology of these diseases, the molecular mechanisms of activation remain unclear. Here we show that oxidized LDL and amyloid-beta trigger inflammatory signaling through a heterodimer of Toll-like receptors 4 and 6. Assembly of this newly identified heterodimer is regulated by signals from the scavenger receptor CD36, a common receptor for these disparate ligands. Our results identify CD36-TLR4-TLR6 activation as a common molecular mechanism by which atherogenic lipids and amyloid-beta stimulate sterile inflammation and suggest a new model of TLR heterodimerization triggered by coreceptor signaling events.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Stewart and colleagues demonstrated that Aβ-mediated release of proinflammatory factors and neurotoxicity partially involved signaling through the CD36/ TLR4/TRL6 complex (108).”
From Microglia in Alzheimer's disease (2017) · cites this paper as [108]
In the citing paper
“CD36 mediates heterodimer formation of TLR4 and TLR6 (REF. 104), and this co-receptor complex upregulates the production of chemokines and cytokines such as pro-IL-1β through the activation of NF-κb.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [105]
In the citing paper
“The Soluble Aβ oligomers and Aβ fibrils can react to various receptors expressed by microglia, including CD14, CD36, CD47, α6β1 integrin, class A scavenger receptor, receptor for advanced glycosylation end products (RAGE) and TLRs (Stewart et al., 2010).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Stewart et al., 2010
In the citing paper
“The binding of Aβ to CD36 (cell surface microglial co-receptor) promotes the TLR4 and/or TLR6 phosphorylation and activation, resulting in the production of inflammatory cytokines and chemokines (Stewart et al., 2010).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Stewart et al., 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Atherosclerosis--an inflammatory disease
Ross, R. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901143400207 · Cited by 21,725
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312
Recognition of microorganisms and activation of the immune response
Medzhitov, R. (2007) · Nature · doi:10.1038/nature06246 · Cited by 2,862
The NALP3 inflammasome is involved in the innate immune response to amyloid-β
Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, K. J., & Golenbock, D. T. (2008) · Nature Immunology · doi:10.1038/ni.1636 · Cited by 2,441
Self-citationOzinsky, A., Underhill, D. M., Fontenot, J. D., Hajjar, A. M., Smith, K. D., Wilson, C. B., Schroeder, L. A., & Aderem, A. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.250476497 · Cited by 2,086
Collaborative Induction of Inflammatory Responses by Dectin-1 and Toll-like Receptor 2
Gantner, B. N., Simmons, R. M., Canavera, S. J., Akira, S., & Underhill, D. M. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021787 · Cited by 1,682
TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β
Kagan, J. C., Su, T., Horng, T., Chow, A. Y., Akira, S., & Medzhitov, R. M. (2008) · Nature Immunology · doi:10.1038/ni1569 · Cited by 1,310
Wyss-Coray (2006) · doi:10.1038/nm1484 · Cited by 1,284
Immortalization of murine microglial cells by a v-raf / v-myc carrying retrovirus
Blasi, E., Barluzzi, R., Bocchini, V., Mazzolla, R., & Bistoni, F. (1990) · Journal of Neuroimmunology · doi:10.1016/0165-5728(90)90073-v · Cited by 1,076
Kunjathoor, V., Febbraio, M., Podrez, E., Moore, K., Andersson, L., Koehn, S. L., Rhee, J. S., Silverstein, R., Hoff, H., & Freeman, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m209649200 · Cited by 1,064
Self-citation
Cited by
Sorted by citations
The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors
Kawai, T., & Akira, S. (2010) · Nature Immunology · doi:10.1038/ni.1863 · Cited by 9,304
Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226
Self-citationNLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., et al. (2010) · Nature · doi:10.1038/nature08938 · Cited by 4,026
Self-citationMechanisms underlying inflammation in neurodegeneration
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010) · Cell · doi:10.1016/j.cell.2010.02.016 · Cited by 3,580
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547
Metadata
- Authors
- Stewart, C. R., Stuart, L. M., Wilkinson, K., van Gils, J. M., Deng, J., Halle, A., Rayner, K. J., Boyer, L., Zhong, R., Frazier, W. A., Lacy-Hulbert, A., Khoury, J. E., Golenbock, D. T., & Moore, K. J.
- Affiliations
- Harvard University (US)
- University of Massachusetts Chan Medical School (US)
- Washington University in St. Louis (US)
- Corresponding author
- Moore, Kathryn J
- ORCID
- Venue
- Nature Immunology
- Published
- 2009-12-27
- Volume
- 11
- Issue
- 2
- Pages
- 155-161
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC2809046
- OpenAlex
- W2045772297
- Cited by
- 1,513
- References
- 42
- Citations by year
- 2026: 53 · 2025: 69 · 2024: 107 · 2023: 74 · 2022: 108 · 2021: 96 · 2020: 102 · 2019: 97 · 2018: 99 · 2017: 94 · 2016: 98 · 2015: 108 · 2014: 81 · 2013: 92 · 2012: 104
- FWCI
- 33.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Wellcome Trust (068089)
- National Institute on Aging (R01AG20255, R01AG020255, R01AG032349)
- National Institute of Allergy and Infectious Diseases (R01AI079198)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- National Institute of Neurological Disorders and Stroke (R01NS059005)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- CD36, TLR4, TLR6, sterile inflammation, oxidized LDL, amyloid-beta, atherosclerosis, Alzheimer's disease, innate immune activation
- MeSH terms
- Animals, Cell Line, Humans, Inflammation, Lipoproteins, LDL, Mice, Inbred C57BL, Blotting, Western, Signal Transduction, Gene Expression, Amyloid beta-Peptides, Microglia, Mice, Knockout, Chemokines, CD36 Antigens, Reverse Transcriptase Polymerase Chain Reaction, Immunoprecipitation, Atherosclerosis, Toll-Like Receptor 4, Toll-Like Receptor 6, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
