A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells

Bouchon, Axel; Hernández-Munain, Cristina; Cella, Marina; Colonna, Marco

doi:10.1084/jem.194.8.1111

Cited by 460Immunotherapy and Immune ResponsesImmune Response and InflammationInflammation biomarkers and pathways

A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells

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Bouchon, Axel, Hernández-Munain, Cristina, Cella, Marina, Colonna, Marco·2001·The Journal of Experimental Medicine

DOI 10.1084/jem.194.8.1111PMC PMC2193511

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Abstract

Gene targeting of the adaptor molecule DAP12 in mice caused abnormal distribution and impaired antigen presentation capacity of dendritic cells (DCs). However, the DAP12-associated receptors expressed on DCs and their functions have not been identified yet. Here we show that the triggering receptor expressed on myeloid cells-2 (TREM-2) is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12. TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase. In contrast to Toll-like receptor-mediated signaling, TREM2/DAP12 stimulation is independent of nuclear factor-kappaB and p38 stress-activated protein kinase. This novel DC activation pathway may regulate DC homeostasis and amplify DC responses to pathogens, explaining the phenotype observed in DAP12-deficient mice.

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TREM2 associates with DAP12 to induce signal transduction, including recruitment and activation of SYK and calcium flux.
“TREM2 associates with the immunoreceptor tyrosine-based activation motif (ITAM)–containing adaptor protein DAP12 to induce signal transduction, including recruitment and activation of spleen tyrosine kinase (SYK) and calcium flux24,25.”
From PLCγ2 regulates TREM2 signalling and integrin-mediated adhesion and migration of human iPSC-derived macrophages (2021) · cites this paper as [25]
The Results (page not specified) show that TREM-2 associates with DAP12 and that TREM-2 ligation causes calcium flux in human monocyte-derived dendritic cells. The Discussion identifies DAP12 as an ITAM-containing adaptor and reports PTK and ERK signaling, but our copy does not show recruitment or activation of SYK by TREM-2. (LLM, conf=0.88)
Experimental — accuracy not yet measured
TREM2 is induced in human monocytes and mouse bone marrow cells upon exposure to GM-CSF and CSF-1.
“We have previously shown that TREM2 is induced in human monocytes and mouse bone marrow cells upon exposure to GM-CSF and CSF-1 (Bouchon et al., 2001; Turnbull et al., 2006).”
From TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy (2020) · cites this paper as Bouchon et al., 2001
The Results section on immature monocyte-derived dendritic cells reports high TREM-2 expression after human monocytes were cultured with GM-CSF and IL-4. It does not report induction in mouse bone marrow cells or by CSF-1; in fact, TREM-2 was undetectable in human monocyte-derived macrophages cultured with M-CSF. No page number is available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
TREM2 expression was first observed in macrophages and dendritic cells, but not granulocytes or monocytes.
“TREM2 expression was first observed in macrophages and dendritic cells, but not granulocytes or monocytes (9–11).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [10]

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Glucocorticoids drive human CD8+ T cell differentiation towards a phenotype with high IL-10 and reduced IL-4, IL-5 and IL-13 production
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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 · see citing works
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 · see citing works
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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 · see citing works
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 · see citing works
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 · see citing works
Cutting Edge: TREM-2 Attenuates Macrophage Activation
Turnbull, I. R., Gilfillan, S., Cella, M., Aoshi, T., Miller, M., Piccio, L., Hernandez, M., & Colonna, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.6.3520 · Cited by 688 · see citing works
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TREMs in the immune system and beyond
Colonna, M. (2003) · Nature Reviews Immunology · doi:10.1038/nri1106 · Cited by 701 · see citing works
Self-citation
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 · see citing works
TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy
Molgora, M., Esaulova, E., Vermi, W., Hou, J., Chen, Y., Luo, J., Brioschi, S., Bugatti, M., Omodei, A. S., Ricci, B., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.013 · Cited by 656 · see citing works
“Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling.”
InfluentialSelf-citation
Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)
Atagi, Y., Liu, C.-C., Painter, M. M., Chen, X.-F., Verbeeck, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.679043 · Cited by 587 · see citing works
sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early‐stage Alzheimer's disease and associate with neuronal injury markers
Suárez‐Calvet, M., Kleinberger, G., Araque Caballero, M. Á., Brendel, M., Rominger, A., Alcolea, D., Fortea, J., Lleó, A., Blesa, R., Gispert, J. D., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201506123 · Cited by 522 · see citing works
New insights into the role of TREM2 in Alzheimer’s disease
Gratuze, M., Leyns, C. E. G., & Holtzman, D. M. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0298-9 · Cited by 489 · see citing works
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 · see citing works
Self-citation
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 · see citing works
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 · see citing works
Cutting Edge: Inhibition of TLR and FcR Responses in Macrophages by Triggering Receptor Expressed on Myeloid Cells (TREM)-2 and DAP12
Hamerman, J. A., Jarjoura, J. R., Humphrey, M. B., Nakamura, M. C., Seaman, W. E., & Lanier, L. L. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.4.2051 · Cited by 440 · see citing works
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 · see citing works
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The biology of TREM receptors
Colonna, M. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00837-1 · Cited by 394 · see citing works
Self-citation
Heterogeneous expression of the triggering receptor expressed on myeloid cells‐2 on adult murine microglia
Schmid, C. D., Sautkulis, L. N., Danielson, P. E., Cooper, J., Hasel, K. W., Hilbush, B. S., Sutcliffe, J. G., & Carson, M. J. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01243.x · Cited by 351 · see citing works
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 · see citing works
Self-citation
Coding variants in TREM2 increase risk for Alzheimer's disease
Jin, S. C., Benitez, B. A., Karch, C. M., Cooper, B., Skorupa, T., Carrell, D., Norton, J. B., Hsu, S., Harari, O., Cai, Y., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu277 · Cited by 314 · see citing works
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 · see citing works
Sequential Proteolytic Processing of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) Protein by Ectodomain Shedding and γ-Secretase-dependent Intramembranous Cleavage
Wunderlich, P., Glebov, K., Kemmerling, N., Tien, N. T., Neumann, H., & Walter, J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.517540 · Cited by 296 · see citing works
Altered microglial response to Aβ plaques in APPPS1-21 mice heterozygous for TREM2
Ulrich, J. D., Finn, M. B., Wang, Y., Shen, A., Mahan, T. E., Jiang, H., Stewart, F. R., Piccio, L., Colonna, M., & Holtzman, D. M. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-20 · Cited by 302 · see citing works
Self-citation
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 · see citing works
The cellular response in neuroinflammation: The role of leukocytes, microglia and astrocytes in neuronal death and survival
Carson, M. J., Cameron Thrash, J., & Walter, B. (2006) · Clinical Neuroscience Research · doi:10.1016/j.cnr.2006.09.004 · Cited by 299 · see citing works
Alzheimer's disease‐associated TREM2 variants exhibit either decreased or increased ligand‐dependent activation
Song, W., Hooli, B., Mullin, K., Jin, S. C., Cella, M., Ulland, T. K., Wang, Y., Tanzi, R. E., & Colonna, M. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.07.004 · Cited by 297 · see citing works
Self-citation
Emerging roles of innate and adaptive immunity in Alzheimer’s disease
Chen, X., & Holtzman, D. M. (2022) · Immunity · doi:10.1016/j.immuni.2022.10.016 · Cited by 297 · see citing works
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 · see citing works
Self-citation
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 · see citing works
“Soluble TREM2 also increased transcription of inflammatory cytokines in microglia through NF-κB activation [109], a pathway that was not previously reported to be activated by cellular TREM2 signaling [88].”
Background
Age-related increases in PGD2 expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice
Zhao, J., Zhao, J., Legge, K., & Perlman, S. (2011) · Journal of Clinical Investigation · doi:10.1172/jci59777 · Cited by 265 · see citing works
Dendritic and Natural Killer Cells Cooperate in the Control/Switch of Innate Immunity
Zitvogel, L. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20012040 · Cited by 268 · see citing works
Impact of TREM2R47H variant on tau pathology–induced gliosis and neurodegeneration
Gratuze, M., Leyns, C. E. G., Sauerbeck, A. D., St-Pierre, M.-K., Xiong, M., Kim, N., Serrano, J. R., Tremblay, M.-È., Kummer, T. T., Colonna, M., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci138179 · Cited by 252 · see citing works
Self-citation
Essential role of the microglial triggering receptor expressed on myeloid cells-2 (TREM2) for central nervous tissue immune homeostasis
Neumann, H., & Takahashi, K. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.11.032 · Cited by 249 · see citing works
Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions
Liu, W., Taso, O., Wang, R., Bayram, S., Graham, A. C., Garcia-Reitboeck, P., Mallach, A., Andrews, W. D., Piers, T. M., Botia, J. A., et al. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa209 · Cited by 214 · see citing works
“TREM2 expression was first observed in macrophages and dendritic cells, but not granulocytes or monocytes (Bouchon et al. 2000; Bouchon et al. 2001; Daws et al. 2001).”
Background
Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model
Meilandt, W. J., Ngu, H., Gogineni, A., Lalehzadeh, G., Lee, S.-H., Srinivasan, K., Imperio, J., Wu, T., Weber, M., Kruse, A. J., et al. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.1871-19.2019 · Cited by 210 · see citing works
“…described roles for Trem2 in osteoclast function (Cella et al., 2003; Paloneva et al., 2003), AKT and mTOR signaling (Ulland et al., 2017), attenuation of proinflammatory macrophage activation (Turnbull et al., 2006), chemotaxis (Mazaheri et al., 2017), and DAP12 signaling (Bouchon et al., 2001).”
Background
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 · see citing works
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 · see citing works
TREM2 in CNS homeostasis and neurodegenerative disease
Painter, M. M., Atagi, Y., Liu, C.-C., Rademakers, R., Xu, H., Fryer, J. D., & Bu, G. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0040-9 · Cited by 169 · see citing works
The Trem2 R47H Alzheimer's risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans
Xiang, X., Piers, T. M., Wefers, B., Zhu, K., Mallach, A., Brunner, B., Kleinberger, G., Song, W., Colonna, M., Herms, J., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0280-6 · Cited by 170 · see citing works
Self-citation
TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function
Humphrey, M. B., Daws, M. R., Spusta, S. C., Niemi, E. C., Torchia, J. A., Lanier, L. L., Seaman, W. E., & Nakamura, M. C. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.051016 · Cited by 162 · see citing works
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 · see citing works
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 · see citing works
<scp>TREM</scp>2 Protein Expression Changes Correlate with <scp>A</scp>lzheimer's Disease Neurodegenerative Pathologies in Post‐Mortem Temporal Cortices
Lue, L., Schmitz, C. T., Serrano, G., Sue, L. I., Beach, T. G., & Walker, D. G. (2015) · Brain Pathology · doi:10.1111/bpa.12190 · Cited by 154 · see citing works
TREM2 is associated with increased risk for Alzheimer’s disease in African Americans
Jin, S. C., Carrasquillo, M. M., Benitez, B. A., Skorupa, T., Carrell, D., Patel, D., Lincoln, S., Krishnan, S., Kachadoorian, M., Reitz, C., et al. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0016-9 · Cited by 153 · see citing works
Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease
Giraldo, M., Lopera, F., Siniard, A. L., Corneveaux, J. J., Schrauwen, I., Carvajal, J., Muñoz, C., Ramirez-Restrepo, M., Gaiteri, C., Myers, A. J., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.02.016 · Cited by 147 · see citing works
Distinct Signaling Pathways Regulate TREM2 Phagocytic and NFκB Antagonistic Activities
Yao, H., Coppola, K., Schweig, J. E., Crawford, F., Mullan, M., & Paris, D. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00457 · Cited by 110 · see citing works
The intracellular domain of CD44 promotes the fusion of macrophages
Cui, W. (2006) · Blood · doi:10.1182/blood-2005-05-1902 · Cited by 110 · see citing works
Structure, expression pattern and biological activity of molecular complex TREM-2/DAP12
Paradowska-Gorycka, A., & Jurkowska, M. (2013) · Human Immunology · doi:10.1016/j.humimm.2013.02.003 · Cited by 103 · see citing works
Shifting paradigms: The central role of microglia in Alzheimer’s disease
Schwabe, T., Srinivasan, K., & Rhinn, H. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104962 · Cited by 84 · see citing works
Immunopathogenic mechanisms and immunoregulatory therapies in MASLD
He, Y., Chen, Y., Qian, S., van Der Merwe, S., Dhar, D., Brenner, D. A., & Tacke, F. (2025) · Cellular & Molecular Immunology · doi:10.1038/s41423-025-01307-5 · Cited by 81 · see citing works
“TREM2 was ﬁ rst cloned from human PBMCs in 2000 [32, 33].”
The innate immune system in Alzheimer's disease
Boutajangout, A., & Wisniewski, T. (2013) · International Journal of Cell Biology · doi:10.1155/2013/576383 · Cited by 69 · see citing works
Microglia, Trem2, and Neurodegeneration
Shi, Q., Gutierrez, R. A., & Bhat, M. A. (2025) · The Neuroscientist · doi:10.1177/10738584241254118 · Cited by 69 · see citing works
What happens to microglial TREM2 in Alzheimer’s disease: Immunoregulatory turned into immunopathogenic?
Lue, L.-F., Schmitz, C., & Walker, D. G. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.09.050 · Cited by 63 · see citing works
Behavioral and transcriptomic analysis of Trem2-null mice: not all knockout mice are created equal
Kang, S. S., Kurti, A., Baker, K. E., Liu, C.-C., Colonna, M., Ulrich, J. D., Holtzman, D. M., Bu, G., & Fryer, J. D. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddx366 · Cited by 62 · see citing works
Self-citation
Innate Immune Response Gene Expression Profiles of N9 Microglia Are Pathogen-Type Specific
McKimmie, C. S., Roy, D., Forster, T., & Fazakerley, J. K. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.03.012 · Cited by 51 · see citing works
Regulation of microglial survival and proliferation in health and diseases
Ulland, T. K., Wang, Y., & Colonna, M. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2016.03.011 · Cited by 43 · see citing works
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Alzheimer’s disease: rare variants with large effect sizes
Del-Aguila, J. L., Koboldt, D. C., Black, K., Chasse, R., Norton, J., Wilson, R. K., & Cruchaga, C. (2015) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2015.07.008 · Cited by 41 · see citing works
PLCγ2 regulates TREM2 signalling and integrin-mediated adhesion and migration of human iPSC-derived macrophages
Obst, J., Hall-Roberts, H. L., Smith, T. B., Kreuzer, M., Magno, L., Di Daniel, E., Davis, J. B., & Mead, E. (2021) · Scientific Reports · doi:10.1038/s41598-021-96144-7 · Cited by 36 · see citing works
Neutral or Detrimental Effects of TREM2 Agonist Antibodies in Preclinical Models of Alzheimer’s Disease and Multiple Sclerosis
Etxeberria, A., Shen, Y.-A. A., Vito, S., Silverman, S. M., Imperio, J., Lalehzadeh, G., Soung, A. L., Du, C., Xie, L., Choy, M. K., et al. (2024) · The Journal of Neuroscience · doi:10.1523/jneurosci.2347-23.2024 · Cited by 34 · see citing works
The Linker for Activation of B Cells (LAB)/Non-T Cell Activation Linker (NTAL) Regulates Triggering Receptor Expressed on Myeloid Cells (TREM)-2 Signaling and Macrophage Inflammatory Responses Independently of the Linker for Activation of T Cells
Whittaker, G. C., Orr, S. J., Quigley, L., Hughes, L., Francischetti, I. M. B., Zhang, W., & McVicar, D. W. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.038398 · Cited by 33 · see citing works
TREM2: Keeping Pace With Immune Checkpoint Inhibitors in Cancer Immunotherapy
Qiu, H., Shao, Z., Wen, X., Jiang, J., Ma, Q., Wang, Y., Huang, L., Ding, X., & Zhang, L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.716710 · Cited by 32 · see citing works
Contributions of triggering-receptor-expressed-on-myeloid-cells-2 to neurological diseases
Han, J., Wang, M., Ren, M., & Lou, H. (2017) · International Journal of Neuroscience · doi:10.1080/00207454.2016.1264072 · Cited by 30 · see citing works
THY-Tau22 mouse model accumulates more tauopathy at late stage of the disease in response to microglia deactivation through TREM2 deficiency
Vautheny, A., Duwat, C., Aurégan, G., Joséphine, C., Hérard, A.-S., Jan, C., Mitja, J., Gipchtein, P., Gaillard, M.-C., Buée, L., et al. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105398 · Cited by 28 · see citing works
A split-luciferase complementation, real-time reporting assay enables monitoring of the disease-associated transmembrane protein TREM2 in live cells
Varnum, M. M., Clayton, K. A., Yoshii-Kitahara, A., Yonemoto, G., Koro, L., Ikezu, S., & Ikezu, T. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.759159 · Cited by 22 · see citing works

Authors: Bouchon, A., Hernández-Munain, C., Cella, M., & Colonna, M.
Affiliations: aBasel Institute for Immunology, CH-4005 Basel, Switzerland
ORCID: Cella, Marina
Colonna, Marco
Venue: The Journal of Experimental Medicine
Publisher: Rockefeller University Press
Published: 2001-10-15
Volume: 194
Issue: 8
Pages: 1111-1122
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.194.8.1111
PMC: PMC2193511
OpenAlex: W2114829829
Cited by: 460
References: 92
Citations by year: 2026: 12 · 2025: 20 · 2024: 21 · 2023: 20 · 2022: 26 · 2021: 23 · 2020: 25 · 2019: 15 · 2018: 21 · 2017: 21 · 2016: 17 · 2015: 22 · 2014: 24 · 2013: 15 · 2012: 11
FWCI: 6.06
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: cc-by-nc-sa
Locations: The Journal of Experimental Medicine (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords: DAP12, TREM2, dendritic cell maturation, dendritic cell survival, monocyte-derived dendritic cells, tyrosine kinase signaling, ERK signaling, antigen presentation
MeSH terms: NF-KappaB Inhibitor alpha, Triggering Receptor Expressed on Myeloid Cells-1, Animals, Histocompatibility Antigens Class II, Cell Differentiation, Cell Line, Cell Survival, Dendritic Cells, DNA-Binding Proteins, Enzyme Activation, Hematopoietic Stem Cells, Humans, Membrane Glycoproteins, Membrane Proteins, Mice, Inbred BALB C, Monocytes, Protein-Tyrosine Kinases, Receptors, Immunologic, Signal Transduction, Antigens, CD, Up-Regulation, NF-kappa B, CD40 Antigens, Receptors, Chemokine, Mitogen-Activated Protein Kinase 1, I-kappa B Proteins, Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Adaptor Proteins, Signal Transducing, Mice, B7-2 Antigen, Receptors, CCR7

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A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells

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