The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
IRAK-M Is a Negative Regulator of Toll-like Receptor Signaling
Open accessAbstract
Toll-like receptors (TLRs) detect microorganisms and protect multicellular organisms from infection. TLRs transduce their signals through MyD88 and the serine/threonine kinase IRAK. The IRAK family consists of two active kinases, IRAK and IRAK-4, and two inactive kinases, IRAK-2 and IRAK-M. IRAK-M expression is restricted to monocytes/macrophages, whereas other IRAKs are ubiquitous. We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. IRAK-M(-/-) cells exhibited increased cytokine production upon TLR/IL-1 stimulation and bacterial challenge, and IRAK-M(-/-) mice showed increased inflammatory responses to bacterial infection. Endotoxin tolerance, a protection mechanism against endotoxin shock, was significantly reduced in IRAK-M(-/-) cells. Thus, IRAK-M regulates TLR signaling and innate immune homeostasis.
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.
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
A Toll-like receptor recognizes bacterial DNA
Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Matsumoto, M., Hoshino, K., Wagner, H., Takeda, K., et al. (2000) · Nature · doi:10.1038/35047123 · Cited by 6,491
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129
Toll-like receptors: critical proteins linking innate and acquired immunity
Akira, S., Takeda, K., & Kaisho, T. (2001) · Nature Immunology · doi:10.1038/90609 · Cited by 4,777
Innate Immunity: The Virtues of a Nonclonal System of Recognition
Medzhitov, R., & Janeway, C. A. (1997) · Cell · doi:10.1016/s0092-8674(00)80412-2 · Cited by 2,434
Self-citation
Cited by
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312
Hayden, M. S., & Ghosh, S. (2004) · Genes & Development · doi:10.1101/gad.1228704 · Cited by 3,842
LPS/TLR4 signal transduction pathway
Lu, Y.-C., Yeh, W.-C., & Ohashi, P. S. (2008) · Cytokine · doi:10.1016/j.cyto.2008.01.006 · Cited by 3,301
The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling
O'Neill, L. A. J., & Bowie, A. G. (2007) · Nature Reviews Immunology · doi:10.1038/nri2079 · Cited by 2,667
Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity
Saeed, S., Quintin, J., Kerstens, H. H. D., Rao, N. A., Aghajanirefah, A., Matarese, F., Cheng, S.-C., Ratter, J., Berentsen, K., van der Ent, M. A., et al. (2014) · Science · doi:10.1126/science.1251086 · Cited by 1,761
Negative regulation of Toll-like receptor-mediated immune responses
Liew, F. Y., Xu, D., Brint, E. K., & O'Neill, L. A. J. (2005) · Nature Reviews Immunology · doi:10.1038/nri1630 · Cited by 1,509
Endotoxin tolerance: new mechanisms, molecules and clinical significance
Biswas, S. K., & Lopez-Collazo, E. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.07.009 · Cited by 1,318
Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4
Pålsson‐McDermott, E. M., & O'Neill, L. A. J. (2004) · Immunology · doi:10.1111/j.1365-2567.2004.01976.x · Cited by 1,254
Hayden, M. S., West, A. P., & Ghosh, S. (2006) · Oncogene · doi:10.1038/sj.onc.1209943 · Cited by 1,178
Akt Signaling Pathway in Macrophage Activation and M1/M2 Polarization
Vergadi, E., Ieronymaki, E., Lyroni, K., Vaporidi, K., & Tsatsanis, C. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601515 · Cited by 1,148
Helical Assembly in the MyD88-IRAK4-IRAK2 Complex in TLR/IL-1R Signalling
Lin, S.-C., Lo, Y.-C., & Wu, H. (2010) · Nature · doi:10.1038/nature09121 · Cited by 1,111
Christensen, S. R., Shupe, J., Nickerson, K., Kashgarian, M., Flavell, R. A., & Shlomchik, M. J. (2006) · Immunity · doi:10.1016/j.immuni.2006.07.013 · Cited by 1,090
Self-citationmRNA is an endogenous ligand for toll-like receptor 3
Karikó, K., Ni, H., Capodici, J., Lamphier, M., & Weissman, D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310175200 · Cited by 1,062
Hyaluronan as an Immune Regulator in Human Diseases
Jiang, D., Liang, J., & Noble, P. W. (2011) · Physiological Reviews · doi:10.1152/physrev.00052.2009 · Cited by 1,060
Lv, M., Chen, M., Zhang, R., Zhang, W., Wang, C., Zhang, Y., Wei, X., Guan, Y., Liu, J., Feng, K., et al. (2020) · Cell Research · doi:10.1038/s41422-020-00395-4 · Cited by 1,040
Sheedy, F. J., Palsson-McDermott, E., Hennessy, E. J., Martin, C., O'Leary, J. J., Ruan, Q., Johnson, D. S., Chen, Y., & O'Neill, L. A. J. (2010) · Nature Immunology · doi:10.1038/ni.1828 · Cited by 1,005
Weber, A., Wasiliew, P., & Kracht, M. (2010) · Science Signaling · doi:10.1126/scisignal.3105cm1 · Cited by 962
IL-1 pathways in inflammation and human diseases
Gabay, C., Lamacchia, C., & Palmer, G. (2010) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2010.4 · Cited by 897
Toll‐like receptors and adaptor molecules in liver disease: Update†
Seki, E., & Brenner, D. A. (2008) · Hepatology · doi:10.1002/hep.22306 · Cited by 722
SOCS1/JAB Is a Negative Regulator of LPS-Induced Macrophage Activation
Kinjyo, I., Hanada, T., Inagaki-Ohara, K., Mori, H., Aki, D., Ohishi, M., Yoshida, H., Kubo, M., & Yoshimura, A. (2002) · Immunity · doi:10.1016/s1074-7613(02)00446-6 · Cited by 630
Dysregulation of brain and choroid plexus cell types in severe COVID-19
Yang, A. C., Kern, F., Losada, P. M., Agam, M. R., Maat, C. A., Schmartz, G. P., Fehlmann, T., Stein, J. A., Schaum, N., Lee, D. P., et al. (2021) · Nature · doi:10.1038/s41586-021-03710-0 · Cited by 620
The Kinase Akt1 Controls Macrophage Response to Lipopolysaccharide by Regulating MicroRNAs
Androulidaki, A., Iliopoulos, D., Arranz, A., Doxaki, C., Schworer, S., Zacharioudaki, V., Margioris, A. N., Tsichlis, P. N., & Tsatsanis, C. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.024 · Cited by 581
Ancuta, P., Kamat, A., Kunstman, K. J., Kim, E.-Y., Autissier, P., Wurcel, A., Zaman, T., Stone, D., Mefford, M., Morgello, S., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002516 · Cited by 499
Targeting TGFβ signal transduction for cancer therapy
Liu, S., Ren, J., & ten Dijke, P. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00436-9 · Cited by 413
“IL1 receptor-associated kinase M (IRAKM) is a potent negative regulator of Toll-like receptor (TLR) signaling and is predominantly expressed in macrophages.(178) By inducing IRAK-M expression and antagonizing TLR signaling, TGFβ protects tumors from the potential TLR-mediated antitumor activities of macrophages.”
BackgroundKinase inhibition in autoimmunity and inflammation
Zarrin, A. A., Bao, K., Lupardus, P., & Vucic, D. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0082-8 · Cited by 431
Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors
Chuang, T.-H., & Ulevitch, R. J. (2004) · Nature Immunology · doi:10.1038/ni1066 · Cited by 374
MAP kinase phosphatase 1 controls innate immune responses and suppresses endotoxic shock
Zhao, Q., Wang, X., Nelin, L. D., Yao, Y., Matta, R., Manson, M. E., Baliga, R. S., Meng, X., Smith, C. V., Bauer, J. A., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20051794 · Cited by 370
ZIP8 Regulates Host Defense through Zinc-Mediated Inhibition of NF-κB
Liu, M.-J., Bao, S., Gálvez-Peralta, M., Pyle, C. J., Rudawsky, A. C., Pavlovicz, R. E., Killilea, D. W., Li, C., Nebert, D. W., Wewers, M. D., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.01.009 · Cited by 367
Microbial recognition by Toll-like receptors
Takeda, K., & Akira, S. (2004) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2003.10.002 · Cited by 285
Cellular and molecular pathways of renal repair after acute kidney injury
Kumar, S. (2018) · Kidney International · doi:10.1016/j.kint.2017.07.030 · Cited by 271
PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)
He, M., Cao, C., Ni, Z., Liu, Y., Song, P., Hao, S., He, Y., Sun, X., & Rao, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00999-9 · Cited by 283
Cao, S., Liu, J., Song, L., & Ma, X. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3484 · Cited by 244
Yanguas‐Casás, N., Barreda‐Manso, M. A., Nieto‐Sampedro, M., & Romero‐Ramírez, L. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.25742 · Cited by 223
Zhou, H., Huang, X., Cui, H., Luo, X., Tang, Y., Chen, S., Wu, L., & Shen, N. (2010) · Blood · doi:10.1182/blood-2010-04-280156 · Cited by 230
Restraint of inflammatory signaling by interdependent strata of negative regulatory pathways
Murray, P. J., & Smale, S. T. (2012) · Nature Immunology · doi:10.1038/ni.2391 · Cited by 170
Lipopolysaccharide-Induced Memory Impairment in Rats: a Model of Alzheimer’s Disease
ZAKARIA, R., WAN YAACOB, W. M. H., OTHMAN, Z., LONG, I., AHMAD, A. H., & AL-RAHBI, B. (2017) · Physiological Research · doi:10.33549/physiolres.933480 · Cited by 167
TGF-β-induced IRAK-M expression in tumor-associated macrophages regulates lung tumor growth
Standiford, T. J., Kuick, R., Bhan, U., Chen, J., Newstead, M., & Keshamouni, V. G. (2011) · Oncogene · doi:10.1038/onc.2010.619 · Cited by 151
TLRs: Professor Mechnikov, sit on your hat
O'Neill, L. A. J. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.10.005 · Cited by 140
An, H., Xu, H., Zhang, M., Zhou, J., Feng, T., Qian, C., Qi, R., & Cao, X. (2005) · Blood · doi:10.1182/blood-2005-01-0191 · Cited by 140
Coats, S. R., Reife, R. A., Bainbridge, B. W., Pham, T.-T. T., & Darveau, R. P. (2003) · Infection and Immunity · doi:10.1128/iai.71.12.6799-6807.2003 · Cited by 138
Izuishi, K., Tsung, A., Jeyabalan, G., Critchlow, N. D., Li, J., Tracey, K. J., Demarco, R. A., Lotze, M. T., Fink, M. P., Geller, D. A., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.12.7154 · Cited by 116
Prostaglandin E 2 as a Regulator of Immunity to Pathogens
Martínez-Colón, G. J., & Moore, B. B. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.12.008 · Cited by 109
Hacking the host: exploitation of macrophage polarization by intracellular bacterial pathogens
Thiriot, J. D., Martinez-Martinez, Y. B., Endsley, J. J., & Torres, A. G. (2020) · Pathogens and Disease · doi:10.1093/femspd/ftaa009 · Cited by 103
Postinfluenza bacterial pneumonia: Host defenses gone awry
Ballinger, M. N., & Standiford, T. J. (2010) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2010.0049 · Cited by 103
A20 Inhibits Toll-Like Receptor 2– and 4–Mediated Interleukin-8 Synthesis in Airway Epithelial Cells
Gon, Y., Asai, Y., Hashimoto, S., Mizumura, K., Jibiki, I., Machino, T., Ra, C., & Horie, T. (2004) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2003-0438oc · Cited by 102
Fajstova, A., Galanova, N., Coufal, S., Malkova, J., Kostovcik, M., Cermakova, M., Pelantova, H., Kuzma, M., Sediva, B., Hudcovic, T., et al. (2020) · Cells · doi:10.3390/cells9122701 · Cited by 90
Noncoding RNAs regulate NF-κB signaling to modulate blood vessel inflammation
Cheng, H. S., Njock, M.-S., Khyzha, N., Dang, L. T., & Fish, J. E. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00422 · Cited by 69
Mitochondrial Ubiquitin Ligase MARCH5 Promotes TLR7 Signaling by Attenuating TANK Action
Shi, H.-X., Liu, X., Wang, Q., Tang, P.-P., Liu, X.-Y., Shan, Y.-F., & Wang, C. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002057 · Cited by 67
Sanada, T., Takaesu, G., Mashima, R., Yoshida, R., Kobayashi, T., & Yoshimura, A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806923200 · Cited by 66
Two Human MYD88 Variants, S34Y and R98C, Interfere with MyD88-IRAK4-Myddosome Assembly
George, J., Motshwene, P. G., Wang, H., Kubarenko, A. V., Rautanen, A., Mills, T. C., Hill, A. V. S., Gay, N. J., & Weber, A. N. R. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.159996 · Cited by 66
Epigenetic Regulation of Kupffer Cell Function in Health and Disease
Bennett, H., Troutman, T. D., Sakai, M., & Glass, C. K. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.609618 · Cited by 66
Investigational IRAK-4 inhibitors for the treatment of rheumatoid arthritis
Wiese, M. D., Manning-Bennett, A. T., & Abuhelwa, A. Y. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1752660 · Cited by 58
Deciphering Reparative Processes in the Inflamed Dental Pulp
El karim, I. A., Cooper, P. R., About, I., Tomson, P. L., Lundy, F. T., & Duncan, H. F. (2021) · Frontiers in Dental Medicine · doi:10.3389/fdmed.2021.651219 · Cited by 46
Hulsmans, M., Geeraert, B., Arnould, T., Tsatsanis, C., & Holvoet, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062253 · Cited by 39
STAC2 negatively regulates osteoclast formation by targeting the RANK signaling complex
Jeong, E., Choi, H. K., Park, J. H., & Lee, S. Y. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0048-5 · Cited by 35
Metadata
- Authors
- Kobayashi, K., Hernandez, L. D., Galán, J. E., Janeway, C. A., Medzhitov, R., & Flavell, R. A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2002-07
- Volume
- 110
- Issue
- 2
- Pages
- 191-202
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W4248219898
- Cited by
- 1,286
- References
- 4
- FWCI
- 20.81
- Type
- journal article
- Language
- en
- Open access
- bronze
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
