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  • Review Article
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TREMs in the immune system and beyond

Nature Reviews Immunology volume 3, pages 445–453 (2003)Cite this article

Key Points

  • Myeloid-cell activation is controlled by many families of receptors, each including activating and inhibitory isoforms.

  • Triggering receptors expressed by myeloid cells (TREMs) are encoded by a gene cluster on human chromosome 6 and mouse chromosome 17.

  • TREM1 is associated with the DAP12 adaptor and amplifies granulocytic and monocytic inflammatory responses during bacteria and fungus infections.

  • Blocking TREM1 function reduces mortality in experimental models of sepsis.

  • TREM2 can associate with the DAP12 adaptor and activates monocyte-derived dendritic cells.

  • TREM2 promotes the differentiation of osteoclasts and glial cells from monocytic precursors.

  • Rare null mutations of TREM2 in humans cause Nasu-Hakola disease, an autosomic recessive disorder that is characterized by bone cysts and demyelination of the central nervous system, resulting in bone fractures and presenile dementia.

Abstract

Triggering receptors expressed by myeloid cells (TREMs) belong to a rapidly expanding family of receptors that include activating and inhibitory isoforms encoded by a gene cluster linked to the MHC. TREM1 and TREM2 activate myeloid cells by signalling through the adaptor protein DAP12. TREM1 triggers phagocyte secretion of pro-inflammatory chemokines and cytokines, amplifying the inflammation that is induced by bacteria and fungi. TREM2 activates monocyte-derived dendritic cells and regulates osteoclast development. Remarkably, TREM2 deficiency leads to a severe disease that is characterized by bone cysts and demyelination of the central nervous system, which results in dementia, implying that the function of TREM2 extends beyond the immune system.

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Figure 1: Organization of the human and mouse TREM gene cluster.
Figure 2: Schematic presentation of the role of TREM1 in inflammatory responses.
Figure 3: TREM regulation of myeloid-cell differentiation.

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References

  1. Hoffmann, J. A., Kafatos, F. C., Janeway, C. A. & Ezekowitz, R. A. Phylogenetic perspectives in innate immunity. Science 284, 1313–1318 (1999).

    Article  CAS  PubMed  Google Scholar 

  2. Medzhitov, R. Toll-like receptors and innate immunity. Nature Rev. Immunol. 1, 135–145 (2001).

    Article  CAS  Google Scholar 

  3. Poltorak, A. et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085–2088 (1998).

    Article  CAS  PubMed  Google Scholar 

  4. Akira, S., Takeda, K. & Kaisho, T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nature Immunol. 2, 675–680 (2001).

    Article  CAS  Google Scholar 

  5. Aderem, A. & Underhill, D. M. Mechanisms of phagocytosis in macrophages. Annu. Rev. Immunol. 17, 593–623 (1999).

    Article  CAS  PubMed  Google Scholar 

  6. Linehan, S. A., Martinez-Pomares, L. & Gordon, S. Mannose receptor and scavenger receptor: two macrophage pattern recognition receptors with diverse functions in tissue homeostasis and host defense. Adv. Exp. Med. Biol. 479, 1–14 (2000).

    CAS  PubMed  Google Scholar 

  7. Brown, G. D. et al. Dectin-1 is a major β-glucan receptor on macrophages. J. Exp. Med. 196, 407–412 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Barrington, R., Zhang, M., Fischer, M. & Carroll, M. C. The role of complement in inflammation and adaptive immunity. Immunol. Rev. 180, 5–15 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Fraser, I. P., Koziel, H. & Ezekowitz, R. A. The serum mannose-binding protein and the macrophage mannose receptor are pattern recognition molecules that link innate and adaptive immunity. Semin. Immunol. 10, 363–372 (1998).

    Article  CAS  PubMed  Google Scholar 

  10. Lanier, L. L. NK cell receptors. Annu. Rev. Immunol. 16, 359–393 (1998).

    Article  CAS  PubMed  Google Scholar 

  11. Dietrich, J., Nakajima, H. & Colonna, M. Human inhibitory and activating Ig-like receptors which modulate the function of myeloid cells. Microbes Infect. 2, 323–329 (2000).

    Article  CAS  PubMed  Google Scholar 

  12. Oldenborg, P. A. et al. Role of CD47 as a marker of self on red blood cells. Science 288, 2051–2054 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Wright, G. J. et al. Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function. Immunity 13, 233–242 (2000).

    Article  CAS  PubMed  Google Scholar 

  14. Hoek, R. M. et al. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 290, 1768–1771 (2000).

    Article  CAS  PubMed  Google Scholar 

  15. Barclay, A. N., Wright, G. J., Brooke, G. & Brown, M. H. CD200 and membrane protein interactions in the control of myeloid cells. Trends Immunol. 23, 285–290 (2002).

    Article  CAS  PubMed  Google Scholar 

  16. Crocker, P. R. & Varki, A. Siglecs, sialic acids and innate immunity. Trends Immunol. 22, 337–342 (2001).

    Article  CAS  PubMed  Google Scholar 

  17. Trowsdale, J. Genetic and functional relationships between MHC and NK receptor genes. Immunity 15, 363–374 (2001).

    Article  CAS  PubMed  Google Scholar 

  18. Tomasello, E., Blery, M., Vely, E. & Vivier, E. Signaling pathways engaged by NK cell receptors: double concerto for activating receptors, inhibitory receptors and NK cells. Semin. Immunol. 12, 139–147 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Arase, H., Mocarski, E. S., Campbell, A. E., Hill, A. B. & Lanier, L. L. Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 296, 1323–1326 (2002).

    Article  CAS  PubMed  Google Scholar 

  20. Smith, H. R. et al. Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Proc. Natl Acad. Sci. USA 99, 8826–8831 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bauer, S. et al. Activation of NK cells and T cells by NKG2D, a receptor for stress- inducible MICA. Science 285, 727–729 (1999).

    Article  CAS  PubMed  Google Scholar 

  22. Diefenbach, A., Jamieson, A. M., Liu, S. D., Shastri, N. & Raulet, D. H. Ligands for the murine NKG2D receptor: expression by tumor cells and activation of NK cells and macrophages. Nature Immunol. 1, 119–126 (2000).

    Article  CAS  Google Scholar 

  23. Cerwenka, A. et al. Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice. Immunity 12, 721–727 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Bouchon, A., Dietrich, J. & Colonna, M. Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J. Immunol. 164, 4991–4995 (2000). This paper reported the original cloning of the triggering receptors expressed by myeloid cells (TREMs).

    Article  CAS  PubMed  Google Scholar 

  25. Bouchon, A., Hernandez-Munain, C., Cella, M. & Colonna, M. A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells. J. Exp. Med. 194, 1111–1122 (2001). A paper that characterized the function of TREM2 in dendritic cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. McVicar, D. W. et al. DAP12-mediated signal transduction in natural killer cells. A dominant role for the Syk protein-tyrosine kinase. J. Biol. Chem. 273, 32934–32942 (1998).

    Article  CAS  PubMed  Google Scholar 

  27. Gingras, M. C., Lapillonne, H. & Margolin, J. F. TREM-1, MDL-1, and DAP12 expression is associated with a mature stage of myeloid development. Mol. Immunol. 38, 817–824 (2002).

    Article  CAS  PubMed  Google Scholar 

  28. Daws, M. R., Lanier, L. L., Seaman, W. E. & Ryan, J. C. Cloning and characterization of a novel mouse myeloid DAP12-associated receptor family. Eur. J. Immunol. 31, 783–791 (2001). The first group to characterize mouse Trems.

    Article  CAS  PubMed  Google Scholar 

  29. Chung, D. H., Seaman, W. E. & Daws, M. R. Characterization of TREM-3, an activating receptor on mouse macrophages: definition of a family of single Ig domain receptors on mouse chromosome 17. Eur. J. Immunol. 32, 59–66 (2002).

    Article  CAS  PubMed  Google Scholar 

  30. Cantoni, C. et al. NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily. J. Exp. Med. 189, 787–796 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Jackson, D. G., Hart, D. N., Starling, G. & Bell, J. I. Molecular cloning of a novel member of the immunoglobulin gene superfamily homologous to the polymeric immunoglobulin receptor. Eur. J. Immunol. 22, 1157–1163 (1992).

    Article  CAS  PubMed  Google Scholar 

  32. Green, B. J., Clark, G. J. & Hart, D. N. The CMRF-35 mAb recognizes a second leukocyte membrane molecule with a domain similar to the poly Ig receptor. Int. Immunol. 10, 891–899 (1998).

    Article  CAS  PubMed  Google Scholar 

  33. Speckman, R. A. et al. Novel immunoglobulin superfamily gene cluster, mapping to a region of human chromosome 17q25, linked to psoriasis susceptibility. Hum. Genet. 112, 34–41 (2003).

    Article  CAS  PubMed  Google Scholar 

  34. Wu, J., Cherwinski, H., Spies, T., Philips, J. H. & Lanier, L. L. DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes in natural killer cells. J. Exp. Med. 192, 1059–1068 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Allcock, R. J., Barrow, A. D., Forbes, S., Beck, S. & Trowsdale, J. The human TREM gene cluster at 6p21.2 encodes both activating and inhibitory single IgV domain receptors and includes NKp44. Eur. J. Immunol. 33, 567–577 (2003).

    Article  CAS  PubMed  Google Scholar 

  36. Washington, A. V., Quigley, L. & McVicar, D. W. Initial characterization of TREM-like transcript (TLT)-1: a putative inhibitory receptor within the TREM cluster. Triggering receptors expressed on myeloid cells. Blood 100, 3822–3824 (2002).

    Article  CAS  PubMed  Google Scholar 

  37. Colonna, M. & Facchetti, F. TREM-1: a new player in acute inflammatory responses. J. Infect. Dis. (in the press).

  38. Bouchon, A., Facchetti, F., Weigand, M. A. & Colonna, M. TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature 410, 1103–1107 (2001). Identification of the pro-inflammatory function of TREM1.

    Article  CAS  PubMed  Google Scholar 

  39. Bleharski, J. R. et al. A role for triggering receptor expressed on myeloid cells-1 in host defense during the early-induced and adaptive phases of the immune response. J. Immunol. 170, 3812–3818 (2003).

    Article  CAS  PubMed  Google Scholar 

  40. Lucas, M. et al. Massive inflammatory syndrome and lymphocytic immunodeficiency in KARAP/DAP12-transgenic mice. Eur. J. Immunol. 32, 2653–2663 (2002).

    Article  CAS  PubMed  Google Scholar 

  41. Wang, H. et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 285, 248–251 (1999).

    Article  CAS  PubMed  Google Scholar 

  42. Bernhagen, J. et al. MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature 365, 756–759 (1993).

    Article  CAS  PubMed  Google Scholar 

  43. Tracey, K. J. & Abraham, E. From mouse to man: or what have we learned about cytokine-based anti-inflammatory therapies? Shock 11, 224–225 (1999).

    Article  CAS  PubMed  Google Scholar 

  44. Ware, L. B. & Matthay, M. A. The acute respiratory distress syndrome. N. Engl. J. Med. 342, 1334–1349 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Banchereau, J. & Steinman, R. M. Dendritic cells and the control of immunity. Nature 392, 245–252 (1998).

    Article  CAS  PubMed  Google Scholar 

  46. Regnault, A. et al. Fcγ receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J. Exp. Med. 189, 371–380 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Tomasello, E. et al. Combined natural killer cell and dendritic cell functional deficiency in KARAP/DAP12 loss-of-function mutant mice. Immunity 13, 355–364 (2000).

    Article  CAS  PubMed  Google Scholar 

  48. Bakker, A. B. et al. DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming. Immunity 13, 345–353 (2000).

    Article  CAS  PubMed  Google Scholar 

  49. Dietrich, J., Cella, M., Seiffert, M., Buhring, H. J. & Colonna, M. Cutting edge: signal-regulatory protein β1 is a DAP12-associated activating receptor expressed in myeloid cells. J. Immunol. 164, 9–12 (2000).

    Article  CAS  PubMed  Google Scholar 

  50. Hakola, H. P., Jarvi, O. H. & Sourander, P. Osteodysplasia polycystica hereditaria combined with sclerosing leucoencephalopathy, a new entity of the dementia praesenilis group. Acta Neurol. Scand. 46, S79 (1970).

    Article  Google Scholar 

  51. Nasu, T., Tsukahara, Y. & Terayama, K. A lipid metabolic disease — 'membranous lipodystrophy' — an autopsy case demonstrating numerous peculiar membrane-structures composed of compound lipid in bone and bone marrow and various adipose tissues. Acta Pathol. Jpn 23, 539–558 (1973).

    CAS  PubMed  Google Scholar 

  52. Verloes, A. et al. Nasu-Hakola syndrome: polycystic lipomembranous osteodysplasia with sclerosing leucoencephalopathy and presenile dementia. J. Med. Genet. 34, 753–757 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kitajima, I. et al. Nasu-Hakola disease (membranous lipodystrophy). Clinical, histopathological and biochemical studies of three cases. J. Neurol. Sci. 91, 35–52 (1989).

    Article  CAS  PubMed  Google Scholar 

  54. Pekkarinen, P. et al. Assignment of the locus for PLO-SL, a frontal-lobe dementia with bone cysts, to 19q13. Am. J. Hum. Genet. 62, 362–372 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Pekkarinen, P. et al. Fine-scale mapping of a novel dementia gene, PLOSL, by linkage disequilibrium. Genomics 54, 307–315 (1998).

    Article  CAS  PubMed  Google Scholar 

  56. Paloneva, J. et al. Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts. Nature Genet. 25, 357–361 (2000).

    Article  CAS  PubMed  Google Scholar 

  57. Kondo, T. et al. Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): Three genetic forms. Neurology 59, 1105–1107 (2002).

    Article  CAS  PubMed  Google Scholar 

  58. Kaifu, T. et al. Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice. J. Clin. Invest. 111, 323–332 (2003). This study characterizes the role of DAP12 in the development of osteoclasts and oligodendrocytes in vivo and in vitro.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Paloneva, J. et al. Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. Am. J. Hum. Genet. 71, 656–662 (2002). Original identification of TREM2 mutations as the basis of Nasu-Hakola disease.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Teitelbaum, S. L. Bone resorption by osteoclasts. Science 289, 1504–1508 (2000).

    Article  CAS  PubMed  Google Scholar 

  61. Wong, B. R., Josien, R. & Choi, Y. TRANCE is a TNF family member that regulates dendritic cell and osteoclast function. J. Leukocyte Biol. 65, 715–724 (1999).

    Article  CAS  PubMed  Google Scholar 

  62. Schmid, C. D. et al. Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia. J. Neurochem. 83, 1309–1320 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Kreutzberg, G. W. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 19, 312–318 (1996).

    Article  CAS  PubMed  Google Scholar 

  64. Daws, M. R., Sullam, P. M., Niemi, E. C., Chen, T. T. & Seaman, W. E. Pattern recognition by TREM-2: binding of anionic ligands. J. Immunol. (in the press). The first identification of a TREM2 ligand.

  65. Aoki, N. et al. The role of the DAP12 signal in mouse myeloid differentiation. J. Immunol. 165, 3790–3796 (2000).

    Article  CAS  PubMed  Google Scholar 

  66. Aoki, N. et al. DAP12 ITAM motif regulates differentiation and apoptosis in M1 leukemia cells. Biochem. Biophys. Res. Commun. 291, 296–304 (2002).

    Article  CAS  PubMed  Google Scholar 

  67. Samaridis, J. & Colonna, M. Cloning of novel immunoglobulin superfamily receptors expressed on human myeloid and lymphoid cells: structural evidence for new stimulatory and inhibitory pathways. Eur. J. Immunol. 27, 660–665 (1997).

    Article  CAS  PubMed  Google Scholar 

  68. Colonna, M. et al. A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells. J. Exp. Med. 186, 1809–1818 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Cosman, D. et al. A novel immunoglobulin superfamily receptor for cellular and viral MHC class I molecules. Immunity 7, 273–282 (1997).

    Article  CAS  PubMed  Google Scholar 

  70. Colonna, M. et al. Human myelomonocytic cells express an inhibitory receptor for classical and nonclassical MHC class I molecules. J. Immunol. 160, 3096–3100 (1998).

    CAS  PubMed  Google Scholar 

  71. Borges, L., Hsu, M. L., Fanger, N., Kubin, M. & Cosman, D. A family of human lymphoid and myeloid Ig-like receptors, some of which bind to MHC class I molecules. J. Immunol. 159, 5192–5196 (1997).

    CAS  PubMed  Google Scholar 

  72. Allen, R. L., Raine, T., Haude, A., Trowsdale, J. & Wilson, M. J. Leukocyte receptor complex-encoded immunomodulatory receptors show differing specificity for alternative HLA-B27 structures. J. Immunol. 167, 5543–5547 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Nakajima, H., Samaridis, J., Angman, L. & Colonna, M. Human myeloid cells express an activating ILT receptor (ILT1) that associates with Fc receptor γ-chain. J. Immunol. 162, 5–8 (1999).

    CAS  PubMed  Google Scholar 

  74. Kubagawa, H., Burrows, P. D. & Cooper, M. D. A novel pair of immunoglobulin-like receptors expressed by B cells and myeloid cells. Proc. Natl Acad. Sci. USA 94, 5261–5266 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kharitonenkov, A. et al. A family of proteins that inhibit signalling through tyrosine kinase receptors. Nature 386, 181–186 (1997).

    Article  CAS  PubMed  Google Scholar 

  76. Brown, E. J. & Frazier, W. A. Integrin-associated protein (CD47) and its ligands. Trends Cell Biol. 11, 130–135 (2001).

    Article  CAS  PubMed  Google Scholar 

  77. Oldenborg, P. A. et al. Role of CD47 as a marker of self on red blood cells. Science 288, 2051–2054 (2000).

    Article  CAS  PubMed  Google Scholar 

  78. Dietrich, J., Cella, M., Seiffert, M., Buhring, H. J. & Colonna, M. Cutting edge: signal-regulatory protein β1 is a DAP12-associated activating receptor expressed in myeloid cells. J. Immunol. 164, 9–12 (2000).

    Article  CAS  PubMed  Google Scholar 

  79. Tomasello, E. et al. Association of signal-regulatory proteins β with KARAP/DAP-12. Eur. J. Immunol. 30, 2147–2156 (2000).

    Article  CAS  PubMed  Google Scholar 

  80. Wright, G. J. et al. Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function. Immunity 13, 233–242 (2000).

    Article  CAS  PubMed  Google Scholar 

  81. Hoek, R. M. et al. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 290, 1768–1771 (2000).

    Article  CAS  PubMed  Google Scholar 

  82. Barclay, A. N., Wright, G. J., Brooke, G. & Brown, M. H. CD200 and membrane protein interactions in the control of myeloid cells. Trends Immunol. 23, 285–290 (2002).

    Article  CAS  PubMed  Google Scholar 

  83. Fournier, N. et al. FDF03, a novel inhibitory receptor of the immunoglobulin superfamily, is expressed by human dendritic and myeloid cells. J. Immunol. 165, 1197–1209 (2000).

    Article  CAS  PubMed  Google Scholar 

  84. Mousseau, D. D., Banville, D., L'Abbe, D., Bouchard, P. & Shen, S. H. PILRα, a novel immunoreceptor tyrosine-based inhibitory motif-bearing protein, recruits SHP-1 upon tyrosine phosphorylation and is paired with the truncated counterpart PILRβ. J. Biol. Chem. 275, 4467–4474 (2000).

    Article  CAS  PubMed  Google Scholar 

  85. Cantoni, C. et al. Molecular and functional characterization of IRp60, a member of the immunoglobulin superfamily that functions as an inhibitory receptor in human NK cells. Eur. J. Immunol. 29, 3148–3159 (1999).

    Article  CAS  PubMed  Google Scholar 

  86. Bakker, A. B., Baker, E., Sutherland, G. R., Phillips, J. H. & Lanier, L. L. Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells. Proc. Natl Acad. Sci. USA 96, 9792–9796 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

I would like to thank S. Gilfillan and W. Barchet for helpful comments.

Author information

Authors and Affiliations

  1. Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, 63110, Missouri, USA

    Marco Colonna

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DATABASES

LocusLink

CBL

CCL2

CCL3

CCL7

CCR7

CD1A

CD3ζ

CD16

CD40L

DAP12

GM-CSF

GRB2

H60

HMG1

ICAM1

IFN-γ

IL-1α

IL-1β

IL-4

IL-8

IL-10

JNK

MCSF

MICA

MICB

MIF

NF-κB

NKp44

PTK

SHP1

SIRP-β1

SYK

TGF-β

TNF

TRANCE

ZAP70

OMIM

Nasu-Hakola disease

FURTHER INFORMATION

LILR nomenclature web site

KIR nomenclature web site

Glossary

MICROGLIA

Bone-marrow-derived macrophage lineage cells that are present in the CNS.

CAECAL LIGATION AND PUNCTURE

An experimental model of polymicrobial sepsis that is induced by ligation and perforation of the caecum.

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Colonna, M. TREMs in the immune system and beyond. Nat Rev Immunol 3, 445–453 (2003). https://doi.org/10.1038/nri1106

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