Toll-like receptor 9–dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE
10.1038/ni1457
Crossref journal-article
Springer Science and Business Media LLC
Nature Immunology (297)
Bibliography

Tian, J., Avalos, A. M., Mao, S.-Y., Chen, B., Senthil, K., Wu, H., Parroche, P., Drabic, S., Golenbock, D., Sirois, C., Hua, J., An, L. L., Audoly, L., La Rosa, G., Bierhaus, A., Naworth, P., Marshak-Rothstein, A., Crow, M. K., Fitzgerald, K. A., … Coyle, A. J. (2007). Toll-like receptor 9–dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nature Immunology, 8(5), 487–496.

Authors 22
  1. Jane Tian (first)
  2. Ana Maria Avalos (additional)
  3. Su-Yau Mao (additional)
  4. Bo Chen (additional)
  5. Kannaki Senthil (additional)
  6. Herren Wu (additional)
  7. Peggy Parroche (additional)
  8. Stacey Drabic (additional)
  9. Douglas Golenbock (additional)
  10. Cherilyn Sirois (additional)
  11. Jing Hua (additional)
  12. Ling Ling An (additional)
  13. Laurent Audoly (additional)
  14. Greg La Rosa (additional)
  15. Angelika Bierhaus (additional)
  16. Peter Naworth (additional)
  17. Ann Marshak-Rothstein (additional)
  18. Mary K Crow (additional)
  19. Katherine A Fitzgerald (additional)
  20. Eicke Latz (additional)
  21. Peter A Kiener (additional)
  22. Anthony J Coyle (additional)
References 65 Referenced 1,107
  1. Mok, C.C. & Lau, C.S. Pathogenesis of systemic lupus erythematosus. J. Clin. Pathol. 56, 481–490 (2003). (10.1136/jcp.56.7.481) / J. Clin. Pathol. by CC Mok (2003)
  2. Denny, M.F. et al. Accelerated macrophage apoptosis induces autoantibody formation and organ damage in systemic lupus erythematosus. J. Immunol. 176, 2095–2104 (2006). (10.4049/jimmunol.176.4.2095) / J. Immunol. by MF Denny (2006)
  3. Robak, E., Sysa-Jedrzejowska, A., Robak, T. & Smolewski, P. Peripheral blood lymphocyte apoptosis and circulating dendritic cells in patients with systemic lupus erythematosus: correlation with immunological status and disease-related symptoms. Clin. Rheumatol. 25, 225–233 (2006). (10.1007/s10067-005-1163-0) / Clin. Rheumatol. by E Robak (2006)
  4. ter Borg, E.J., Horst, G., Hummel, E.J., Limburg, P.C. & Kallenberg, C.G. Measurement of increases in anti-double-stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus. A long-term, prospective study. Arthritis Rheum. 33, 634–643 (1990). (10.1002/art.1780330505) / Arthritis Rheum. by EJ ter Borg (1990)
  5. Magnusson, M., Magnusson, S., Vallin, H., Ronnblom, L. & Alm, G.V. Importance of CpG dinucleotides in activation of natural IFN-α-producing cells by a lupus-related oligodeoxynucleotide. Scand. J. Immunol. 54, 543–550 (2001). (10.1046/j.1365-3083.2001.01018.x) / Scand. J. Immunol. by M Magnusson (2001)
  6. Sano, H. et al. Binding properties of human anti-DNA antibodies to cloned human DNA fragments. Scand. J. Immunol. 30, 51–63 (1989). (10.1111/j.1365-3083.1989.tb01188.x) / Scand. J. Immunol. by H Sano (1989)
  7. Bauer, S. et al. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc. Natl. Acad. Sci. USA 98, 9237–9242 (2001). (10.1073/pnas.161293498) / Proc. Natl. Acad. Sci. USA by S Bauer (2001)
  8. Latz, E. et al. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat. Immunol. 5, 190–198 (2004). (10.1038/ni1028) / Nat. Immunol. by E Latz (2004)
  9. Krieg, A.M. Therapeutic potential of Toll-like receptor 9 activation. Nat. Rev. Drug Discov. 5, 471–484 (2006). (10.1038/nrd2059) / Nat. Rev. Drug Discov. by AM Krieg (2006)
  10. Ishii, K.J. & Akira, S. Innate immune recognition of, and regulation by, DNA. Trends Immunol. 27, 525–532 (2006). (10.1016/j.it.2006.09.002) / Trends Immunol. by KJ Ishii (2006)
  11. Wu, C.C., Lee, J., Raz, E., Corr, M. & Carson, D.A. Necessity of oligonucleotide aggregation for toll-like receptor 9 activation. J. Biol. Chem. 279, 33071–33078 (2004). (10.1074/jbc.M311662200) / J. Biol. Chem. by CC Wu (2004)
  12. Barrat, F.J. et al. Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J. Exp. Med. 202, 1131–1139 (2005). (10.1084/jem.20050914) / J. Exp. Med. by FJ Barrat (2005)
  13. Guiducci, C. et al. Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation. J. Exp. Med. 203, 1999–2008 (2006). (10.1084/jem.20060401) / J. Exp. Med. by C Guiducci (2006)
  14. Barton, G.M., Kagan, J.C. & Medzhitov, R. Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nat. Immunol. 7, 49–56 (2006). (10.1038/ni1280) / Nat. Immunol. by GM Barton (2006)
  15. Ronnblom, L., Eloranta, M.L. & Alm, G.V. Role of natural interferon-α producing cells (plasmacytoid dendritic cells) in autoimmunity. Autoimmunity 36, 463–472 (2003). (10.1080/08916930310001602128) / Autoimmunity by L Ronnblom (2003)
  16. Asselin-Paturel, C. & Trinchieri, G. Production of type I interferons: plasmacytoid dendritic cells and beyond. J. Exp. Med. 202, 461–465 (2005). (10.1084/jem.20051395) / J. Exp. Med. by C Asselin-Paturel (2005)
  17. Jego, G. et al. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 19, 225–234 (2003). (10.1016/S1074-7613(03)00208-5) / Immunity by G Jego (2003)
  18. Blanco, P., Palucka, A.K., Gill, M., Pascual, V. & Banchereau, J. Induction of dendritic cell differentiation by IFN-α in systemic lupus erythematosus. Science 294, 1540–1543 (2001). (10.1126/science.1064890) / Science by P Blanco (2001)
  19. Crow, M.K. Interferon pathway activation in systemic lupus erythematosus. Curr. Rheumatol. Rep. 7, 463–468 (2005). (10.1007/s11926-005-0053-4) / Curr. Rheumatol. Rep. by MK Crow (2005)
  20. Gottenberg, J.E. et al. Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjogren's syndrome. Proc. Natl. Acad. Sci. USA 103, 2770–2775 (2006). (10.1073/pnas.0510837103) / Proc. Natl. Acad. Sci. USA by JE Gottenberg (2006)
  21. Bennett, L. et al. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J. Exp. Med. 197, 711–723 (2003). (10.1084/jem.20021553) / J. Exp. Med. by L Bennett (2003)
  22. Stott, K., Tang, G.S., Lee, K.B. & Thomas, J.O. Structure of a complex of tandem HMG boxes and DNA. J. Mol. Biol. 360, 90–104 (2006). (10.1016/j.jmb.2006.04.059) / J. Mol. Biol. by K Stott (2006)
  23. Scaffidi, P., Misteli, T. & Bianchi, M.E. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418, 191–195 (2002). (10.1038/nature00858) / Nature by P Scaffidi (2002)
  24. Wang, H. et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 285, 248–251 (1999). (10.1126/science.285.5425.248) / Science by H Wang (1999)
  25. Qin, S. et al. Role of HMGB1 in apoptosis-mediated sepsis lethality. J. Exp. Med. 203, 1637–1642 (2006). (10.1084/jem.20052203) / J. Exp. Med. by S Qin (2006)
  26. Andersson, U. & Erlandsson-Harris, H. HMGB1 is a potent trigger of arthritis. J. Intern. Med. 255, 344–350 (2004). (10.1111/j.1365-2796.2003.01303.x) / J. Intern. Med. by U Andersson (2004)
  27. Yang, H. et al. Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc. Natl. Acad. Sci. USA 101, 296–301 (2004). (10.1073/pnas.2434651100) / Proc. Natl. Acad. Sci. USA by H Yang (2004)
  28. Kokkola, R. et al. High mobility group box chromosomal protein 1: a novel proinflammatory mediator in synovitis. Arthritis Rheum. 46, 2598–2603 (2002). (10.1002/art.10540) / Arthritis Rheum. by R Kokkola (2002)
  29. Kokkola, R. et al. RAGE is the major receptor for the proinflammatory activity of HMGB1 in rodent macrophages. Scand. J. Immunol. 61, 1–9 (2005). (10.1111/j.0300-9475.2005.01534.x) / Scand. J. Immunol. by R Kokkola (2005)
  30. Park, J.S. et al. High mobility group box 1 protein interacts with multiple Toll-like receptors. Am. J. Physiol. Cell Physiol. 290, C917–C924 (2006). (10.1152/ajpcell.00401.2005) / Am. J. Physiol. Cell Physiol. by JS Park (2006)
  31. Hori, O. et al. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J. Biol. Chem. 270, 25752–25761 (1995). (10.1074/jbc.270.43.25752) / J. Biol. Chem. by O Hori (1995)
  32. Dumitriu, I.E., Baruah, P., Bianchi, M.E., Manfredi, A.A. & Rovere-Querini, P. Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells. Eur. J. Immunol. 35, 2184–2190 (2005). (10.1002/eji.200526066) / Eur. J. Immunol. by IE Dumitriu (2005)
  33. Dumitriu, I.E. et al. Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products. J. Immunol. 174, 7506–7515 (2005). (10.4049/jimmunol.174.12.7506) / J. Immunol. by IE Dumitriu (2005)
  34. Popovic, K. et al. Increased expression of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 in skin lesions of patients with lupus erythematosus. Arthritis Rheum. 52, 3639–3645 (2005). (10.1002/art.21398) / Arthritis Rheum. by K Popovic (2005)
  35. Lakowicz, J.R. On spectral relaxation in proteins. Photochem. Photobiol. 72, 421–437 (2000). (10.1562/0031-8655(2000)072<0421:OSRIP>2.0.CO;2) / Photochem. Photobiol. by JR Lakowicz (2000)
  36. Viglianti, G.A. et al. Activation of autoreactive B cells by CpG dsDNA. Immunity 19, 837–847 (2003). (10.1016/S1074-7613(03)00323-6) / Immunity by GA Viglianti (2003)
  37. Marshak-Rothstein, A. et al. Comparison of CpG s-ODNs, chromatin immune complexes, and dsDNA fragment immune complexes in the TLR9-dependent activation of rheumatoid factor B cells. J. Endotoxin Res. 10, 247–251 (2004). (10.1177/09680519040100040801) / J. Endotoxin Res. by A Marshak-Rothstein (2004)
  38. Hua, J., Kirou, K., Lee, C. & Crow, M.K. Functional assay of type I interferon in systemic lupus erythematosus plasma and association with anti-RNA binding protein autoantibodies. Arthritis Rheum. 54, 1906–1916 (2006). (10.1002/art.21890) / Arthritis Rheum. by J Hua (2006)
  39. Lovgren, 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). (10.1002/art.20254) / Arthritis Rheum. by T Lovgren (2004)
  40. Ehlers, M., Fukuyama, H., McGaha, T.L., Aderem, A. & Ravetch, J.V. TLR9/MyD88 signaling is required for class switching to pathogenic IgG2a and 2b autoantibodies in SLE. J. Exp. Med. 203, 553–561 (2006). (10.1084/jem.20052438) / J. Exp. Med. by M Ehlers (2006)
  41. Goodnow, C.C. Immunology. Discriminating microbe from self suffers a double toll. Science 312, 1606–1608 (2006). (10.1126/science.1129797) / Science by CC Goodnow (2006)
  42. Means, T.K. & Luster, A.D. Toll-like receptor activation in the pathogenesis of systemic lupus erythematosus. Ann. NY Acad. Sci. 1062, 242–251 (2005). (10.1196/annals.1358.027) / Ann. NY Acad. Sci. by TK Means (2005)
  43. Muller, S. et al. New EMBO members' review: the double life of HMGB1 chromatin protein: architectural factor and extracellular signal. EMBO J. 20, 4337–4340 (2001). (10.1093/emboj/20.16.4337) / EMBO J. by S Muller (2001)
  44. Stott, K., Tang, G.S., Lee, K.B. & Thomas, J.O. Structure of a complex of tandem HMG boxes and DNA. J. Mol. Biol. 360, 90–104 (2006). (10.1016/j.jmb.2006.04.059) / J. Mol. Biol. by K Stott (2006)
  45. Napolitani, G., Rinaldi, A., Bertoni, F., Sallusto, F. & Lanzavecchia, A. Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1–polarizing program in dendritic cells. Nat. Immunol. 6, 769–776 (2005). (10.1038/ni1223) / Nat. Immunol. by G Napolitani (2005)
  46. Wang, H., Yang, H. & Tracey, K.J. Extracellular role of HMGB1 in inflammation and sepsis. J. Intern. Med. 255, 320–331 (2004). (10.1111/j.1365-2796.2003.01302.x) / J. Intern. Med. by H Wang (2004)
  47. Li, J. et al. Recombinant HMGB1 with cytokine-stimulating activity. J. Immunol. Methods 289, 211–223 (2004). (10.1016/j.jim.2004.04.019) / J. Immunol. Methods by J Li (2004)
  48. Andersson, U. et al. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J. Exp. Med. 192, 565–570 (2000). (10.1084/jem.192.4.565) / J. Exp. Med. by U Andersson (2000)
  49. Degryse, B. et al. The high mobility group (HMG) boxes of the nuclear protein HMG1 induce chemotaxis and cytoskeleton reorganization in rat smooth muscle cells. J. Cell Biol. 152, 1197–1206 (2001). (10.1083/jcb.152.6.1197) / J. Cell Biol. by B Degryse (2001)
  50. Palumbo, R. et al. Extracellular HMGB1, a signal of tissue damage, induces mesoangioblast migration and proliferation. J. Cell Biol. 164, 441–449 (2004). (10.1083/jcb.200304135) / J. Cell Biol. by R Palumbo (2004)
  51. Fiuza, C. et al. Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells. Blood 101, 2652–2660 (2003). (10.1182/blood-2002-05-1300) / Blood by C Fiuza (2003)
  52. Sappington, P.L. et al. HMGB1 B box increases the permeability of Caco-2 enterocytic monolayers and impairs intestinal barrier function in mice. Gastroenterology 123, 790–802 (2002). (10.1053/gast.2002.35391) / Gastroenterology by PL Sappington (2002)
  53. Sorci, G., Riuzzi, F., Arcuri, C., Giambanco, I. & Donato, R. Amphoterin stimulates myogenesis and counteracts the antimyogenic factors basic fibroblast growth factor and S100B via RAGE binding. Mol. Cell. Biol. 24, 4880–4894 (2004). (10.1128/MCB.24.11.4880-4894.2004) / Mol. Cell. Biol. by G Sorci (2004)
  54. Rong, L.L. et al. Antagonism of RAGE suppresses peripheral nerve regeneration. FASEB J. 18, 1812–1817 (2004). (10.1096/fj.04-1899com) / FASEB J. by LL Rong (2004)
  55. Taguchi, A. et al. Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature 405, 354–360 (2000). (10.1038/35012626) / Nature by A Taguchi (2000)
  56. Popovic, P.J. et al. High mobility group B1 protein suppresses the human plasmacytoid dendritic cell response to TLR9 agonists. J. Immunol. 177, 8701–8707 (2006). (10.4049/jimmunol.177.12.8701) / J. Immunol. by PJ Popovic (2006)
  57. Bonaldi, T. et al. Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J. 22, 5551–5560 (2003). (10.1093/emboj/cdg516) / EMBO J. by T Bonaldi (2003)
  58. Leadbetter, E.A. et al. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 416, 603–607 (2002). (10.1038/416603a) / Nature by EA Leadbetter (2002)
  59. Ahmad-Nejad, P. et al. Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur. J. Immunol. 32, 1958–1968 (2002). (10.1002/1521-4141(200207)32:7<1958::AID-IMMU1958>3.0.CO;2-U) / Eur. J. Immunol. by P Ahmad-Nejad (2002)
  60. Ishihara, K., Tsutsumi, K., Kawane, S., Nakajima, M. & Kasaoka, T. The receptor for advanced glycation end-products (RAGE) directly binds to ERK by a D-domain-like docking site. FEBS Lett. 550, 107–113 (2003). (10.1016/S0014-5793(03)00846-9) / FEBS Lett. by K Ishihara (2003)
  61. Kirou, K.A. et al. Activation of the interferon-α pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum. 52, 1491–1503 (2005). (10.1002/art.21031) / Arthritis Rheum. by KA Kirou (2005)
  62. Lovgren, 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). (10.1002/art.20254) / Arthritis Rheum. by T Lovgren (2004)
  63. Vallin, H., Perers, A., Alm, G.V. & Ronnblom, L. Anti-double-stranded DNA antibodies and immunostimulatory plasmid DNA in combination mimic the endogenous IFN-α inducer in systemic lupus erythematosus. J. Immunol. 163, 6306–6313 (1999). (10.4049/jimmunol.163.11.6306) / J. Immunol. by H Vallin (1999)
  64. Walker, J.M., Goodwin, G.H., Johns, E.W., Wietzes, P. & Gaastra, W. A comparison of the amino-terminal sequences of two calf-thymus chromatin non-histone proteins. Int. J. Pept. Protein Res. 9, 220–223 (1977). (10.1111/j.1399-3011.1977.tb03484.x) / Int. J. Pept. Protein Res. by JM Walker (1977)
  65. Chavakis, T. et al. The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J. Exp. Med. 198, 1507–1515 (2003). (10.1084/jem.20030800) / J. Exp. Med. by T Chavakis (2003)
Dates
Type When
Created 18 years, 4 months ago (April 8, 2007, 1:13 p.m.)
Deposited 1 year, 6 months ago (Feb. 13, 2024, 2:23 a.m.)
Indexed 2 days, 13 hours ago (Aug. 21, 2025, 12:40 p.m.)
Issued 18 years, 4 months ago (April 8, 2007)
Published 18 years, 4 months ago (April 8, 2007)
Published Online 18 years, 4 months ago (April 8, 2007)
Published Print 18 years, 3 months ago (May 1, 2007)
Funders 0

None

@article{Tian_2007, title={Toll-like receptor 9–dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE}, volume={8}, ISSN={1529-2916}, url={http://dx.doi.org/10.1038/ni1457}, DOI={10.1038/ni1457}, number={5}, journal={Nature Immunology}, publisher={Springer Science and Business Media LLC}, author={Tian, Jane and Avalos, Ana Maria and Mao, Su-Yau and Chen, Bo and Senthil, Kannaki and Wu, Herren and Parroche, Peggy and Drabic, Stacey and Golenbock, Douglas and Sirois, Cherilyn and Hua, Jing and An, Ling Ling and Audoly, Laurent and La Rosa, Greg and Bierhaus, Angelika and Naworth, Peter and Marshak-Rothstein, Ann and Crow, Mary K and Fitzgerald, Katherine A and Latz, Eicke and Kiener, Peter A and Coyle, Anthony J}, year={2007}, month=apr, pages={487–496} }