The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity

Nature Immunology

Volumn 16, Issue 5, 2015, Pages 495-504

  Ramirez Ortiz, Zaida G ^a   Prasad, Amit ^a   Griffith, Jason W ^a   Pendergraft, William F ^b   Cowley, Glenn S ^c   Root, David E ^c   Tai, Melissa ^a   Luster, Andrew D ^a   El Khoury, Joseph ^a   Hacohen, Nir ^a,c   Means, Terry K ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^c BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INTERFERON; MEMBRANE RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE P38; MYELOID DIFFERENTIATION FACTOR 88; STAT1 PROTEIN; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 13; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 9; TREML4 RECEPTOR; UNCLASSIFIED DRUG; AUTACOID; AUTOANTIBODY; CYTOKINE; IMMUNOGLOBULIN RECEPTOR; MEMBRANE PROTEIN; SMALL INTERFERING RNA; TLR7 PROTEIN, MOUSE; TREML4 PROTEIN, MOUSE;

ARTICLE; AUTOIMMUNITY; CONTROLLED STUDY; CYTOKINE PRODUCTION; ENZYME ACTIVATION; FEMALE; IMMUNE RESPONSE; INFLUENZA VIRUS; MACROPHAGE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; SYSTEMIC LUPUS ERYTHEMATOSUS; VIRUS IMMUNITY; ANIMAL; C57BL MOUSE; CELL CULTURE; GENETICS; HUMAN; IMMUNOLOGY; INNATE IMMUNITY; KNOCKOUT MOUSE; METABOLISM; MURPHY ROTHS LARGE LYMPHOPROLIFERATIVE MOUSE; ORTHOMYXOVIRIDAE; ORTHOMYXOVIRUS INFECTION; PHYSIOLOGY; VIROLOGY;

ANIMALS; AUTOANTIBODIES; AUTOIMMUNITY; CELLS, CULTURED; CYTOKINES; HUMANS; IMMUNITY, INNATE; INFLAMMATION MEDIATORS; INTERFERON TYPE I; LUPUS ERYTHEMATOSUS, SYSTEMIC; MACROPHAGES; MEMBRANE GLYCOPROTEINS; MICE; MICE, INBRED C57BL; MICE, INBRED MRL LPR; MICE, KNOCKOUT; MYELOID DIFFERENTIATION FACTOR 88; ORTHOMYXOVIRIDAE; ORTHOMYXOVIRIDAE INFECTIONS; P38 MITOGEN-ACTIVATED PROTEIN KINASES; RECEPTORS, IMMUNOLOGIC; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; STAT1 TRANSCRIPTION FACTOR; TOLL-LIKE RECEPTOR 7;

EID: 84928543526     PISSN: 15292908     EISSN: 15292916     Source Type: Journal    
DOI: 10.1038/ni.3143     Document Type: Article

References (45)

1. O?Neill, L.A., Golenbock, D. & Bowie, A.G. The history of Toll-like receptors-redefining innate immunity. Nat. Rev. Immunol. 13, 453-460 (2013).
2. Barbalat, R., Ewald, S.E., Mouchess, M.L. & Barton, G.M. Nucleic acid recognition by the innate immune system. Annu. Rev. Immunol. 29, 185-214 (2011).
3. Gay, N.J. & Keith, F.J. Drosophila Toll and IL-1 receptor. Nature 351, 355-356 (1991).
4. Akira, S. & Takeda, K. Toll-like receptor signalling. Nat. Rev. Immunol. 4, 499-511 (2004).
5. Kono, D.H., Baccala, R. & Theofilopoulos, A.N. TLRs and interferons: a central paradigm in autoimmunity. Curr. Opin. Immunol. 25, 720-727 (2013).
6. 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).
7. Turnbull, I.R. et al. Cutting edge: TREM-2 attenuates macrophage activation. J. Immunol. 177, 3520-3524 (2006).
8. Hamerman, J.A. et al. Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. J. Immunol. 177, 2051-2055 (2006).
9. Ornatowska, M. et al. Functional genomics of silencing TREM-1 on TLR4 signaling in macrophages. Am. J. Physiol. Lung Cell. Mol. Physiol. 293, L1377-L1384 (2007).
10. Ford, J.W. & McVicar, D.W. TREM and TREM-like receptors in inflammation and disease. Curr. Opin. Immunol. 21, 38-46 (2009).
11. Washington, A.V. et al. TREM-like transcript-1 protects against inflammation-associated hemorrhage by facilitating platelet aggregation in mice and humans. J. Clin. Invest. 119, 1489-1501 (2009).
12. Guerreiro, R. et al. TREM2 variants in Alzheimer?s disease. N. Engl. J. Med. 368, 117-127 (2013).
13. Jonsson, T. et al. Variant of TREM2 associated with the risk of Alzheimer?s disease. N. Engl. J. Med. 368, 107-116 (2013).
14. Hamerman, J.A., Tchao, N.K., Lowell, C.A. & Lanier, L.L. Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12. Nat. Immunol. 6, 579-586 (2005).
15. Hemmi, H. et al. A new triggering receptor expressed on myeloid cells (Trem) family member, Trem-like 4, binds to dead cells and is a DNAX activation protein 12-linked marker for subsets of mouse macrophages and dendritic cells. J. Immunol. 182, 1278-1286 (2009).
16. N?Diaye, E.N. et al. TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria. J. Cell Biol. 184, 215-223 (2009).
17. Lövgren, T., Eloranta, M.L., Bave, U., Alm, G.V. & Ronnblom, L. Induction of interferon-alpha production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum. 50, 1861-1872 (2004).
18. Pisitkun, P. et al. Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science 312, 1669-1672 (2006).
19. Subramanian, S. et al. A Tlr7 translocation accelerates systemic autoimmunity in murine lupus. Proc. Natl. Acad. Sci. USA 103, 9970-9975 (2006).
20. Deane, J.A. et al. Control of toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation. Immunity 27, 801-810 (2007).
21. Christensen, S.R. et al. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity 25, 417-428 (2006).
22. Berland, R. et al. Toll-like receptor 7-dependent loss of B cell tolerance in pathogenic autoantibody knockin mice. Immunity 25, 429-440 (2006).
23. Wang, C.M. et al. Genetic variations in Toll-like receptors (TLRs 3/7/8) are associated with systemic lupus erythematosus in a Taiwanese population. Sci. Rep. 4, 3792 (2014).
24. Luo, B. et al. Highly parallel identification of essential genes in cancer cells. Proc. Natl. Acad. Sci. USA 105, 20380-20385 (2008).
25. Moffat, J. et al. A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 124, 1283-1298 (2006).
26. Ramirez-Ortiz, Z.G. et al. The scavenger receptor SCARF1 mediates the clearance of apoptotic cells and prevents autoimmunity. Nat. Immunol. 14, 917-926 (2013).
27. Hemmi, H. et al. Treml4, an Ig superfamily member, mediates presentation of several antigens to T cells in vivo, including protective immunity to HER2 protein. J. Immunol. 188, 1147-1155 (2012).
28. Diebold, S.S., Kaisho, T., Hemmi, H., Akira, S. & Reis e Sousa, C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303, 1529-1531 (2004).
29. Ramsauer, K. et al. p38 MAPK enhances STAT1-dependent transcription independently of Ser-727 phosphorylation. Proc. Natl. Acad. Sci. USA 99, 12859-12864 (2002).
30. Luu, K. et al. STAT1 plays a role in TLR signal transduction and inflammatory responses. Immunol. Cell Biol. 92, 761-769 (2014).
31. Ivashkiv, L.B. Cross-regulation of signaling by ITAM-associated receptors. Nat. Immunol. 10, 340-347 (2009).
32. Klesney-Tait, J., Turnbull, I.R. & Colonna, M. The TREM receptor family and signal integration. Nat. Immunol. 7, 1266-1273 (2006).
33. Paradowska-Gorycka, A. & Jurkowska, M. Structure, expression pattern and biological activity of molecular complex TREM-2/DAP12. Hum. Immunol. 74, 730-737 (2013).
34. Paloneva, J. et al. Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts. Nat. Genet. 25, 357-361 (2000).
35. 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).
36. Gibot, S. et al. A soluble form of the triggering receptor expressed on myeloid cells-1 modulates the inflammatory response in murine sepsis. J. Exp. Med. 200, 1419-1426 (2004).
37. Piccio, L. et al. Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation. Brain 131, 3081-3091 (2008).
38. Kleinberger, G. et al. TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci Transl Med. 6, 243ra286 (2014).
39. Sen, S.K. et al. Integrative DNA, RNA, and protein evidence connects TREML4 to coronary artery calcification. Am. J. Hum. Genet. 95, 66-76 (2014).
40. Silbiger, V.N. et al. Novel genes detected by transcriptional profiling from whole-blood cells in patients with early onset of acute coronary syndrome. Clin. Chim. Acta 421, 184-190 (2013).
41. Christensen, S.R. et al. Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus. J. Exp. Med. 202, 321-331 (2005).
42. Herlands, R.A., Christensen, S.R., Sweet, R.A., Hershberg, U. & Shlomchik, M.J. T cell-independent and toll-like receptor-dependent antigen-driven activation of autoreactive B cells. Immunity 29, 249-260 (2008).
43. Nickerson, K.M. et al. TLR9 regulates TLR7- and MyD88-dependent autoantibody production and disease in a murine model of lupus. J. Immunol. 184, 1840-1848 (2010).
44. Barrat, F.J., Meeker, T., Chan, J.H., Guiducci, C. & Coffman, R.L. Treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 leads to reduction of autoantibody production and amelioration of disease symptoms. Eur. J. Immunol. 37, 3582-3586 (2007).
45. Thibault, D.L. et al. IRF9 and STAT1 are required for IgG autoantibody production and B cell expression of TLR7 in mice. J. Clin. Invest. 118, 1417-1426 (2008).