Cited by 440Immune Response and InflammationInflammation biomarkers and pathwaysPhagocytosis and Immune Regulation

The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.

Cutting Edge: Inhibition of TLR and FcR Responses in Macrophages by Triggering Receptor Expressed on Myeloid Cells (TREM)-2 and DAP12

Open access

Hamerman, Jessica A, Jarjoura, Jessica R, Humphrey, Mary Beth, Nakamura, Mary C, Seaman, William E, Lanier, Lewis L·2006·The Journal of Immunology

DOI 10.4049/jimmunol.177.4.2051

Open this paper in CoChat — free account Open PDF

Abstract

DAP12 is an ITAM-containing adapter that associates with receptors in myeloid and NK cells. DAP12-associated receptors can give activation signals leading to cytokine production; however, in some situations, DAP12 inhibits cytokine production stimulated through TLRs and FcRs. Here we show that Triggering Receptor Expressed on Myeloid cells (TREM)-2 is responsible for the DAP12-mediated inhibition in mouse macrophages. A chimeric receptor composed of the extracellular domain of TREM-2 and the cytoplasmic domain of DAP12 inhibited the TLR- and FcR-induced TNF production of DAP12-deficient macrophages, whereas a TREM-1 chimera did not. In wild-type macrophages, TREM-2 knockdown increased TLR-induced TNF production. A TREM-2 Fc fusion protein bound to macrophages, indicating that macrophages express a TREM-2 ligand. Thus, the interaction of TREM-2 and its ligand results in an inhibitory signal that can reduce the inflammatory response.

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

Crossref · 10.4049/jimmunol.177.4.2051

Cites

19 of 19 references verified0 citation errors · 0 not checkable

Statistics

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2
Takahashi, K., Rochford, C. D. P., & Neumann, H. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041611 · Cited by 1,124
TREMs in the immune system and beyond
Colonna, M. (2003) · Nature Reviews Immunology · doi:10.1038/nri1106 · Cited by 701
Mutations in Two Genes Encoding Different Subunits of a Receptor Signaling Complex Result in an Identical Disease Phenotype
Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/342259 · Cited by 683
Association of DAP12 with Activating CD94/NKG2C NK Cell Receptors
Lanier, L. L., Corliss, B. C., Wu, J., & Phillips, J. H. (1998) · Immunity · doi:10.1016/s1074-7613(00)80574-9 · Cited by 560
Self-citation
Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts
Paloneva, J., Kestilä, M., Wu, J., Salminen, A., Böhling, T., Ruotsalainen, V., Hakola, P., Bakker, A. B. H., Phillips, J. H., Pekkarinen, P., et al. (2000) · Nature Genetics · doi:10.1038/77153 · Cited by 460
Self-citation
A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells
Bouchon, A., Hernández-Munain, C., Cella, M., & Colonna, M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.8.1111 · Cited by 460
Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice
Kaifu, T., Nakahara, J., Inui, M., Mishima, K., Momiyama, T., Kaji, M., Sugahara, A., Koito, H., Ujike, A., Nakamura, A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16923 · Cited by 342
Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12
Hamerman, J. A., Tchao, N. K., Lowell, C. A., & Lanier, L. L. (2005) · Nature Immunology · doi:10.1038/ni1204 · Cited by 325
Self-citation
DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features
Paloneva, J., Mandelin, J., Kiialainen, A., Böhling, T., Prudlo, J., Hakola, P., Haltia, M., Konttinen, Y. T., & Peltonen, L. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030027 · Cited by 318
Pattern Recognition by TREM-2: Binding of Anionic Ligands
Daws, M. R., Sullam, P. M., Niemi, E. C., Chen, T. T., Tchao, N. K., & Seaman, W. E. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.2.594 · Cited by 291
Self-citation

Flagged first, then by citations

Show all 19 references

Research works printed but not linked: 19

2000, Immunol. Today, 611
2005, Eur. J. Immunol., 1670
2005, Nat. Immunol., 579
1998, Immunity, 693
2006, J. Bone Miner. Res., 237
2003, J. Immunol., 594
2003, Nat. Rev. Immunol., 445
2001, Eur. J. Immunol., 783
2001, J. Exp. Med., 1111
2002, Am. J. Hum. Genet., 656
2003, J. Clin. Invest., 323
2003, J. Exp. Med., 669
2004, J. Bone Miner. Res., 224
2003, J. Exp. Med., 645
2005, J. Exp. Med., 647
2006, Blood, 2474
2005, Blood, 2076
2000, Nat. Genet., 357
2000, Immunity, 345

Sorted by citations

Microglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676
Microglia Function in the Central Nervous System During Health and Neurodegeneration
Colonna, M., & Butovsky, O. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052358 · Cited by 2,894
Variant of TREM2 Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558
Microglia in Alzheimer’s disease
Hansen, D. V., Hanson, J. E., & Sheng, M. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201709069 · Cited by 1,935
TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer’s Disease Model
Wang, Y., Cella, M., Mallinson, K., Ulrich, J. D., Young, K. L., Robinette, M. L., Gilfillan, S., Krishnan, G. M., Sudhakar, S., Zinselmeyer, B. H., et al. (2015) · Cell · doi:10.1016/j.cell.2015.01.049 · Cited by 1,736
Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668
“Although DAP12 is generally considered to induce activation signal through its ITAM domain, the TREM2/DAP12 complex can also induce inhibitory signals,(240,241) JNK and ERK1/ 2 signaling have been suggested to be involved in this process.(240,242) We still know little about how DAP12 regulates ERK1/2 and JNK signaling.”
Background
Innate immune activation in neurodegenerative disease
Heneka, M. T., Kummer, M. P., & Latz, E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3705 · Cited by 1,437
Signalling through C-type lectin receptors: shaping immune responses
Geijtenbeek, T. B. H., & Gringhuis, S. I. (2009) · Nature reviews. Immunology · doi:10.1038/nri2569 · Cited by 1,449
Cooperation of Toll-like receptor signals in innate immune defence
Trinchieri, G., & Sher, A. (2007) · Nature reviews. Immunology · doi:10.1038/nri2038 · Cited by 1,394
Microglial cell origin and phenotypes in health and disease
Saijo, K., & Glass, C. K. (2011) · Nature Reviews Immunology · doi:10.1038/nri3086 · Cited by 1,100
Microglia in Alzheimer's disease
Sarlus, H., & Heneka, M. T. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90606 · Cited by 911
Innate immunity in Alzheimer's disease
Heneka, M. T., Golenbock, D. T., & Latz, E. (2015) · Nature Immunology · doi:10.1038/ni.3102 · Cited by 902
TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis
Kleinberger, G., Yamanishi, Y., Suárez-Calvet, M., Czirr, E., Lohmann, E., Cuyvers, E., Struyfs, H., Pettkus, N., Wenninger-Weinzierl, A., Mazaheri, F., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009093 · Cited by 798
Neuronal ‘On’ and ‘Off’ signals control microglia
Biber, K., Neumann, H., Inoue, K., & Boddeke, H. W. G. M. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.08.007 · Cited by 787
TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge
Nugent, A. A., Lin, K., van Lengerich, B., Lianoglou, S., Przybyla, L., Davis, S. S., Llapashtica, C., Wang, J., Kim, D. J., Xia, D., et al. (2020) · Neuron · doi:10.1016/j.neuron.2019.12.007 · Cited by 745
Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation States and Aspects of Alzheimer’s Disease Not Evident in Mouse Models
Friedman, B. A., Srinivasan, K., Ayalon, G., Meilandt, W. J., Lin, H., Huntley, M. A., Cao, Y., Lee, S.-H., Haddick, P. C. G., Ngu, H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.066 · Cited by 662
The Physiology, Pathology, and Potential Therapeutic Applications of the TREM2 Signaling Pathway
Deczkowska, A., Weiner, A., & Amit, I. (2020) · Cell · doi:10.1016/j.cell.2020.05.003 · Cited by 648
Lipopolysaccharide-induced blood-brain barrier disruption: Roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit
Banks, W. A., Gray, A. M., Erickson, M. A., Salameh, T. S., Damodarasamy, M., Sheibani, N., Meabon, J. S., Wing, E. E., Morofuji, Y., Cook, D. G., et al. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0434-1 · Cited by 636
Information processing during phagocytosis
Underhill, D. M., & Goodridge, H. S. (2012) · Nature Reviews Immunology · doi:10.1038/nri3244 · Cited by 616
The TREM receptor family and signal integration
Klesney‐Tait, J., Turnbull, I. R., & Colonna, M. (2006) · Nature Immunology · doi:10.1038/ni1411 · Cited by 602
Regulatory T Cells Inhibit Dendritic Cells by Lymphocyte Activation Gene-3 Engagement of MHC Class II
Liang, B., Workman, C., Lee, J., Chew, C., Dale, B. M., Colonna, L., Flores, M., Li, N., Schweighoffer, E., Greenberg, S., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.9.5916 · Cited by 566
Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease
Roy, E. R., Wang, B., Wan, Y.-W., Chiu, G., Cole, A., Yin, Z., Propson, N. E., Xu, Y., Jankowsky, J. L., Liu, Z., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133737 · Cited by 563
Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease
Newcombe, E. A., Camats-Perna, J., Silva, M. L., Valmas, N., Huat, T. J., & Medeiros, R. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1313-3 · Cited by 532
TREM2 sustains microglial expansion during aging and response to demyelination
Poliani, P. L., Wang, Y., Fontana, E., Robinette, M. L., Yamanishi, Y., Gilfillan, S., & Colonna, M. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77983 · Cited by 525
A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia
Hsieh, C. L., Koike, M., Spusta, S. C., Niemi, E. C., Yenari, M., Nakamura, M. C., & Seaman, W. E. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06042.x · Cited by 475
Self-citation
Curcumin Inhibits LPS-Induced Neuroinflammation by Promoting Microglial M2 Polarization via TREM2/TLR4/NF-Κb Pathways in BV2 Cells
Zhang, J., Zheng, Y., Luo, Y., Du, Y., Zhang, X., & Fu, J. (2019) · Molecular Immunology · doi:10.1016/j.molimm.2019.09.020 · Cited by 464
TREM2, microglia, and neurodegenerative diseases
Yeh, F. L., Hansen, D. V., & Sheng, M. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.03.008 · Cited by 440
TREM and TREM-like receptors in inflammation and disease
Ford, J. W., & McVicar, D. W. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.01.009 · Cited by 434
TREM2 in Neurodegenerative Diseases
Jay, T. R., von Saucken, V. E., & Landreth, G. E. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0197-5 · Cited by 427
TREM2 variants: new keys to decipher Alzheimer disease pathogenesis
Colonna, M., & Wang, Y. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.7 · Cited by 418
TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1
Peng, Q., Malhotra, S., Torchia, J. A., Kerr, W. G., Coggeshall, K. M., & Humphrey, M. B. (2010) · Science Signaling · doi:10.1126/scisignal.2000500 · Cited by 413
Self-citation
The biology of TREM receptors
Colonna, M. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00837-1 · Cited by 394
TLR4 Cross-Talk With NLRP3 Inflammasome and Complement Signaling Pathways in Alzheimer's Disease
Yang, J., Wise, L., & Fukuchi, K.-I. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00724 · Cited by 387
Negative signaling by inhibitory receptors: the NK cell paradigm
Long, E. O. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00660.x · Cited by 381
Gene Expression Profiling of Human Decidual Macrophages: Evidence for Immunosuppressive Phenotype
Gustafsson, C., Mjösberg, J., Matussek, A., Geffers, R., Matthiesen, L., Berg, G. E., Sharma, S., Buer, J., & Ernerudh, J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002078 · Cited by 376
TREM-1–expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases
Schenk, M., Bouchon, A., Seibold, F., & Mueller, C. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30602 · Cited by 365
Fc receptor-targeted therapies for the treatment of inflammation, cancer and beyond
Hogarth, P. M., & Pietersz, G. A. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd2909 · Cited by 358
Molecular mediators of macrophage fusion
Helming, L., & Gordon, S. (2009) · Trends in Cell Biology · doi:10.1016/j.tcb.2009.07.005 · Cited by 326
DAP10‐ and DAP12‐associated receptors in innate immunity
Lanier, L. L. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00720.x · Cited by 332
Self-citation
Upregulation of TREM2 Ameliorates Neuropathology and Rescues Spatial Cognitive Impairment in a Transgenic Mouse Model of Alzheimer’s Disease
Jiang, T., Tan, L., Zhu, X.-C., Zhang, Q.-Q., Cao, L., Tan, M.-S., Gu, L.-Z., Wang, H.-F., Ding, Z.-Z., Zhang, Y.-D., et al. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.164 · Cited by 320
Innate Immunity and Neurodegeneration
Labzin, L. I., Heneka, M. T., & Latz, E. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-050715-104343 · Cited by 319
The effects of microglia-associated neuroinflammation on Alzheimer’s disease
Wang, C., Zong, S., Cui, X., Wang, X., Wu, S., Wang, L., Liu, Y., & Lu, Z. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1117172 · Cited by 331
Induction of myelodysplasia by myeloid-derived suppressor cells
Chen, X., Eksioglu, E. A., Zhou, J., Zhang, L., Djeu, J., Fortenbery, N., Epling-Burnette, P., Van Bijnen, S., Dolstra, H., Cannon, J., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67580 · Cited by 316
Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation
Piccio, L. M., Buonsanti, C., Cella, M., Tassi, I., Schmidt, R. E., Fenoglio, C., Rinker, J. R., Naismith, R. T., Panina‐Bordignon, P., Passini, N., et al. (2008) · Brain · doi:10.1093/brain/awn217 · Cited by 311
Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism
Song, W. M., Joshita, S., Zhou, Y., Ulland, T. K., Gilfillan, S., & Colonna, M. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20171529 · Cited by 305
Coactivation of Syk Kinase and MyD88 Adaptor Protein Pathways by Bacteria Promotes Regulatory Properties of Neutrophils
Zhang, X., Majlessi, L., Dériaud, E., Leclerc, C., & Lo‐Man, R. (2009) · Immunity · doi:10.1016/j.immuni.2009.09.016 · Cited by 302
Microglial TREM2/DAP12 signaling: a double-edged sword in neural diseases
Konishi, H., & Kiyama, H. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00206 · Cited by 300
TREM2 regulates microglial cell activation in response to demyelination in vivo
Cantoni, C., Bollman, B., Licastro, D., Xie, M., Mikesell, R., Schmidt, R., Yuede, C. M., Galimberti, D., Olivecrona, G., Klein, R. S., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1388-1 · Cited by 296
Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways in macrophage activation
Hu, X., Chen, J., Wang, L., & Ivashkiv, L. B. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.1206763 · Cited by 293
Efficient colonic mucosal wound repair requires Trem2 signaling
Seno, H., Miyoshi, H., Brown, S. L., Geske, M. J., Colonna, M., & Stappenbeck, T. S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803343106 · Cited by 286
Blockade of TREM‐2 exacerbates experimental autoimmune encephalomyelitis
Piccio, L., Buonsanti, C., Mariani, M., Cella, M., Gilfillan, S., Cross, A. H., Colonna, M., & Panina‐Bordignon, P. (2007) · European Journal of Immunology · doi:10.1002/eji.200636837 · Cited by 284
TREM2-Ligand Interactions in Health and Disease
Kober, D. L., & Brett, T. J. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.04.004 · Cited by 284
“TREM2 responds to tonic stimuli to regulate inflammation—TREM2 and DAP12 reduce inflammatory TLR signals [98, 99] in cultured BMDMs.”
Background
Clearance of cerebral Aβ in Alzheimer’s disease: reassessing the role of microglia and monocytes
Zuroff, L. R., Daley, D. A., Black, K. L., & Koronyo‐Hamaoui, M. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2463-7 · Cited by 292
Activating and inhibitory functions of DAP12
Turnbull, I. R., & Colonna, M. (2007) · Nature Reviews Immunology · doi:10.1038/nri2014 · Cited by 273
Src-family and Syk Kinases in Activating and Inhibitory Pathways in Innate Immune Cells: Signaling Cross TalkPreprint
Lowell, C. A. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a002352 · Cited by 277
Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development
Wang, X., He, Q., Zhou, C., Xu, Y., Liu, D., Fujiwara, N., Kubota, N., Click, A., Henderson, P., Vancil, J., et al. (2023) · Immunity · doi:10.1016/j.immuni.2022.11.013 · Cited by 262
Microglia and aging: the role of the TREM2-DAP12 and CX3CL1-CX3CR1 axes
Mecca, C., Giambanco, I., Donato, R., & Arcuri, C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010318 · Cited by 258
An Alzheimer‐associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function
Schlepckow, K., Kleinberger, G., Fukumori, A., Feederle, R., Lichtenthaler, S. F., Steiner, H., & Haass, C. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707672 · Cited by 266
Systemic infection and inflammation in acute CNS injury and chronic neurodegeneration: Underlying mechanisms
Teeling, J. L., & Perry, V. H. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.07.031 · Cited by 259
TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice
Frank, S., Burbach, G. J., Bonin, M., Walter, M., Streit, W., Bechmann, I., & Deller, T. (2008) · Glia · doi:10.1002/glia.20710 · Cited by 247
The FTD‐like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism
Kleinberger, G., Brendel, M., Mracsko, E. Z., Wefers, B., Groeneweg, L., Xiang, X., Focke, C., Deußing, M., Suárez‐Calvet, M., Mazaheri, F., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201796516 · Cited by 249
TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria
N’Diaye, E.-N., Branda, C., Branda, S. S., Nevarez, L., Colonna, M., Lowell, C. A., Hamerman, J. A., & Seaman, W. E. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200808080 · Cited by 243
Self-citation
Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms
Kober, D. L., Alexander-Brett, J. M., Karch, C. M., Cruchaga, C., Colonna, M., Holtzman, M. J., & Brett, T. J. (2016) · eLife · doi:10.7554/elife.20391 · Cited by 238
TREM-1: intracellular signaling pathways and interaction with pattern recognition receptors
Arts, R. J. W., Joosten, L. A. B., van der Meer, J. W. M., & Netea, M. G. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0312145 · Cited by 242
An Overview of in vitro Methods to Study Microglia
Timmerman, R., Burm, S. M., & Bajramovic, J. J. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00242 · Cited by 243
TREM2 and the neuroimmunology of Alzheimer's disease
Hickman, S. E., & El Khoury, J. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.11.021 · Cited by 221
Amyloid-beta modulates microglial responses by binding to the triggering receptor expressed on myeloid cells 2 (TREM2)
Zhong, L., Wang, Z., Wang, D., Wang, Z., Martens, Y. A., Wu, L., Xu, Y., Wang, K., Li, J., Huang, R., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0247-7 · Cited by 222
Spatiotemporal dynamics of macrophage heterogeneity and a potential function of Trem2hi macrophages in infarcted hearts
Jung, S., Hwang, B., Shin, S. Y., Park, E., Park, S., Kim, C. W., Kim, E., Choo, E. H., Choi, I. J., Świrski, F. K., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32284-2 · Cited by 219
Cross-regulation of signaling by ITAM-associated receptors
Ivashkiv, L. B. (2009) · Nature Immunology · doi:10.1038/ni.1706 · Cited by 219
TREM-2 promotes macrophage survival and lung disease after respiratory viral infection
Wu, K., Byers, D. E., Jin, X., Agapov, E., Alexander-Brett, J., Patel, A. C., Cella, M., Gilfilan, S., Colonna, M., Kober, D. L., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20141732 · Cited by 207
TREM2 in the pathogenesis of AD: a lipid metabolism regulator and potential metabolic therapeutic target
Li, R.-Y., Qin, Q., Yang, H.-C., Wang, Y.-Y., Mi, Y.-X., Yin, Y.-S., Wang, M., Yu, C.-J., & Tang, Y. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00542-y · Cited by 204
The role of TLR activation in inflammation
Sabroe, I., Parker, L. C., Dower, S., & Whyte, M. (2007) · The Journal of Pathology · doi:10.1002/path.2264 · Cited by 205
The TREM-1/DAP12 pathway
Tessarz, A. S., & Cerwenka, A. (2008) · Immunology Letters · doi:10.1016/j.imlet.2007.11.021 · Cited by 202
TREM2 shedding by cleavage at the H157‐S158 bond is accelerated for the Alzheimer's disease‐associated H157Y variant
Thornton, P., Sevalle, J., Deery, M. J., Fraser, G., Zhou, Y., Ståhl, S., Franssen, E. H., Dodd, R. B., Qamar, S., Gomez Perez‐Nievas, B., et al. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707673 · Cited by 200
Plaque-associated human microglia accumulate lipid droplets in a chimeric model of Alzheimer’s disease
Claes, C., Danhash, E. P., Hasselmann, J., Chadarevian, J. P., Shabestari, S. K., England, W. E., Lim, T. E., Hidalgo, J. L. S., Spitale, R. C., Davtyan, H., et al. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00473-0 · Cited by 197
From expression to signaling: Roles of TREM-1 and TREM-2 in innate immunity and bacterial infection
Sharif, O., & Knapp, S. (2008) · Immunobiology · doi:10.1016/j.imbio.2008.07.008 · Cited by 199
Functional Studies of Missense TREM2 Mutations in Human Stem Cell-Derived Microglia
Brownjohn, P. W., Smith, J., Solanki, R., Lohmann, E., Houlden, H., Hardy, J., Dietmann, S., & Livesey, F. J. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.03.003 · Cited by 193
Trem2 promotes foamy macrophage lipid uptake and survival in atherosclerosis
Patterson, M. T., Firulyova, M. M., Xu, Y., Hillman, H., Bishop, C., Zhu, A., Hickok, G. H., Schrank, P. R., Ronayne, C. E., Caillot, Z., et al. (2023) · Nature Cardiovascular Research · doi:10.1038/s44161-023-00354-3 · Cited by 204
The many faces of ITAMs
Underhill, D. M., & Goodridge, H. S. (2007) · Trends in Immunology · doi:10.1016/j.it.2006.12.004 · Cited by 193
Pathways to neurodegeneration: mechanistic insights from GWAS in Alzheimer's disease, Parkinson's disease, and related disorders.
Ramanan, V. K., & Saykin, A. J. (2013) · Europe PMC (PubMed Central) · Cited by 190
The Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome
Petes, C., Odoardi, N., & Gee, K. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01075 · Cited by 177
Temporal gene profiling of the 5XFAD transgenic mouse model highlights the importance of microglial activation in Alzheimer’s disease
Landel, V., Baranger, K., Virard, I., Loriod, B., Khrestchatisky, M., Rivera, S., Benech, P., & Féron, F. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-33 · Cited by 176
Innate Immune Responses to TREM-1 Activation: Overlap, Divergence, and Positive and Negative Cross-Talk with Bacterial Lipopolysaccharide
Dower, K., Ellis, D. K., Saraf, K. A., Jelinsky, S. A., & Lin, L. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.5.3520 · Cited by 181
TREM-2, triggering receptor expressed on myeloid cell-2, negatively regulates TLR responses in dendritic cells
Ito, H., & Hamerman, J. A. (2012) · European Journal of Immunology · doi:10.1002/eji.201141679 · Cited by 173
Self-citation
Inhibitory ITAMs as novel regulators of immunity
Blank, U., Launay, P., Benhamou, M., & Monteiro, R. C. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00832.x · Cited by 175
Human Induced Pluripotent Stem Cell-Derived Microglia-Like Cells Harboring TREM2 Missense Mutations Show Specific Deficits in Phagocytosis
Garcia-Reitboeck, P., Phillips, A., Piers, T. M., Villegas-Llerena, C., Butler, M., Mallach, A., Rodrigues, C., Arber, C. E., Heslegrave, A., Zetterberg, H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.094 · Cited by 162
Genetics ignite focus on microglial inflammation in Alzheimer’s disease
Malik, M., Parikh, I., Vasquez, J. B., Smith, C., Tai, L., Bu, G., LaDu, M. J., Fardo, D. W., Rebeck, G. W., & Estus, S. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0048-1 · Cited by 161
Syk‐coupled C‐type lectin receptors that mediate cellular activation via single tyrosine based activation motifs
Kerrigan, A. M., & Brown, G. D. (2010) · Immunological Reviews · doi:10.1111/j.0105-2896.2009.00882.x · Cited by 167
Microglial TYROBP/DAP12 in Alzheimer's Disease: Transduction of Physiological and Pathological Signals Across TREM2
Haure-Mirande, J.-V., Audrain, M., Ehrlich, M. E., & Gandy, S. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00552-w · Cited by 159
Mouse TCRαβ+CD8αα Intraepithelial Lymphocytes Express Genes That Down-Regulate Their Antigen Reactivity and Suppress Immune Responses
Denning, T. L., Granger, S. W., Mucida, D., Graddy, R., Leclercq, G., Zhang, W., Honey, K., Rasmussen, J. P., Cheroutre, H., Rudensky, A. Y., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.7.4230 · Cited by 158
TREM2 Function in Alzheimer’s Disease and Neurodegeneration
Ulrich, J. D., & Holtzman, D. M. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00313 · Cited by 154
The surface‐exposed chaperone, Hsp60, is an agonist of the microglial TREM2 receptor
Stefano, L., Racchetti, G., Bianco, F., Passini, N., Gupta, R. S., Panina‐Bordignon, P., & Meldolesi, J. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06130.x · Cited by 150
Biomarkers used in Alzheimer’s disease diagnosis, treatment, and prevention
Mahaman, Y. A. R., Embaye, K. S., Huang, F., Li, L., Zhu, F., Wang, J.-Z., Liu, R., Feng, J., & Wang, X. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101544 · Cited by 149
Microglial inflammation and phagocytosis in Alzheimer's disease: Potential therapeutic targets
Nizami, S., Hall‐Roberts, H., Warrier, S., Cowley, S. A., & Di Daniel, E. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14618 · Cited by 147
The extended human leukocyte receptor complex: diverse ways of modulating immune responses
Barrow, A. D., & Trowsdale, J. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00653.x · Cited by 147
Macrophages, Low-Grade Inflammation, Insulin Resistance and Hyperinsulinemia: A Mutual Ambiguous Relationship in the Development of Metabolic Diseases
Püschel, G. P., Klauder, J., & Henkel, J. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11154358 · Cited by 156
CD16 promotes Escherichia coli sepsis through an FcRγ inhibitory pathway that prevents phagocytosis and facilitates inflammation
da Silva, F. P., Aloulou, M., Skurnik, D., Benhamou, M., Andremont, A., Velasco, I. T., Chiamolera, M., Verbeek, J. S., Launay, P., & Monteiro, R. C. (2007) · Nature Medicine · doi:10.1038/nm1665 · Cited by 139
Multiple roles of Lyn kinase in myeloid cell signaling and function
Scapini, P., Pereira, S. E., Zhang, H., & Lowell, C. A. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00758.x · Cited by 135
Soluble TREM2: Innocent bystander or active player in neurological diseases?
Filipello, F., Goldsbury, C., You, S. F., Locca, A., Karch, C. M., & Piccio, L. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105630 · Cited by 134
DAP12 stabilizes the C-terminal fragment of the triggering receptor expressed on myeloid cells-2 (TREM2) and protects against LPS-induced pro-inflammatory response
Zhong, L., Chen, X.-F., Zhang, Z.-L., Wang, Z., Shi, X.-Z., Xu, K., Zhang, Y.-W., Xu, H., & Bu, G. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.645986 · Cited by 133

Authors: Hamerman, J. A., Jarjoura, J. R., Humphrey, M. B., Nakamura, M. C., Seaman, W. E., & Lanier, L. L.
Affiliations: University of California, San Francisco (US)
San Francisco VA Medical Center (US)
ORCID: Hamerman, Jessica A
Humphrey, Mary Beth
Nakamura, Mary C
Lanier, Lewis L
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2006-08
Volume: 177
Issue: 4
Pages: 2051-2055
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.177.4.2051
OpenAlex: W2133084626
Cited by: 440
References: 19
Citations by year: 2026: 13 · 2025: 21 · 2024: 28 · 2023: 15 · 2022: 37 · 2021: 19 · 2020: 17 · 2019: 21 · 2018: 25 · 2017: 25 · 2016: 18 · 2015: 27 · 2014: 28 · 2013: 19 · 2012: 13
FWCI: 10.85
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Veterans Affairs (I01 BX000615)
National Institutes of Health
National Cancer Institute (R01CA087922, CA 87922)
National Institute of Allergy and Infectious Diseases (AI-068129, R01AI068129)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR050038, AR 050038)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords: TREM2, DAP12, macrophages, Toll-like receptor signaling, Fc receptor signaling, TNF production, inhibitory signaling, TREM-1, chimeric receptors, cytokine production, inflammation regulation
MeSH terms: Animals, Cells, Cultured, Ligands, Macrophages, Membrane Glycoproteins, Mice, Inbred C57BL, Receptors, Fc, Receptors, Immunologic, Tumor Necrosis Factor-alpha, Mice, Knockout, Inflammation Mediators, Adaptor Proteins, Signal Transducing, Toll-Like Receptors, 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

Cutting Edge: Inhibition of TLR and FcR Responses in Macrophages by Triggering Receptor Expressed on Myeloid Cells (TREM)-2 and DAP12

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks