Modulating toll-like receptor 7 and 9 responses as therapy for allergy and autoimmunity

Current Allergy and Asthma Reports

Volumn 12, Issue 1, 2012, Pages 8-17

  Matesic, Damir ^a   Lenert, Aleksander ^b   Lenert, Petar ^c  

^a Allergy and Asthma   (United States)

^b LERNER RESEARCH INSTITUTE   (United States)

^c UNIVERSITY OF IOWA   (United States)

Author keywords

Allergy; Animal models of lupus; Asthma; Autoimmunity; Autophagosomes; B cells; Bacterial DNA; Cathepsins; CpG ODN; Endopeptidases; Endosomes; IgE; INH ODN; R 848; Ragweed; Regulatory T cells; SLE; Systemic lupus erythematosus; Th1; Th17; Th2; TLR7; TLR9; Toll like receptor

Indexed keywords

B LYMPHOCYTE RECEPTOR; IMMUNOGLOBULIN E; OLIGONUCLEOTIDE; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 7 AGONIST; TOLL LIKE RECEPTOR 9; TOLL LIKE RECEPTOR 9 AGONIST; TOLL LIKE RECEPTOR AGONIST; UNCLASSIFIED DRUG;

ALLERGIC ASTHMA; ALLERGIC RHINITIS; ARTICLE; AUTOIMMUNITY; AUTOPHAGOSOME; B LYMPHOCYTE; CARBOXY TERMINAL SEQUENCE; HUMAN; IMMEDIATE TYPE HYPERSENSITIVITY; IMMUNE RESPONSE; IMMUNOMODULATION; LIGAND BINDING; NONHUMAN; PLASMA CELL; REGULATORY T LYMPHOCYTE; TH1 CELL; TH17 CELL; TH2 CELL;

AUTOIMMUNE DISEASES; AUTOIMMUNITY; BINDING, COMPETITIVE; HUMANS; HYPERSENSITIVITY; OLIGONUCLEOTIDES; TOLL-LIKE RECEPTOR 7; TOLL-LIKE RECEPTOR 9;

EID: 84857625202     PISSN: 15297322     EISSN: 15346315     Source Type: Journal    
DOI: 10.1007/s11882-011-0233-4     Document Type: Article

References (116)

1. AA Horner JH Van Uden JM Zubeldia, et al. 2001 DNA-based immunotherapeutics for the treatment of allergic disease Immunol Rev 179 102 118 11292014 1:CAS:528:DC%2BD3MXhvFektr8%3D (Pubitemid 32171278)
2. F Meiler S Klunker M Zimmermann, et al. 2008 Distinct regulation of IgE, IgG4 and IgA by T regulatory cells and Toll-like receptors Allergy 63 1455 1463 18925882 1:CAS:528:DC%2BD1cXhsVemsbnM
3. JN Kline AM Krieg 2008 Toll-like receptor 9 activation with CpG oligodeoxynucleotides for asthma therapy Drug News Perspect 21 434 439 19034349 1:CAS:528:DC%2BD1MXitFCmtLc%3D
4. HL Spiegelberg AA Horner K Takabayashi E Raz 2002 Allergen- immunostimulatory oligodeoxynucleotide conjugate: a novel allergoid for immunotherapy Curr Opin Allergy Clin Immunol 2 547 551 14752340 (Pubitemid 36105820)
5. YJ Chang HY Kim LA Albacker, et al. 2011 Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity J Clin Invest 121 57 69 21157038 1:CAS:528:DC%2BC3MXis1yguw%3D%3D This article describes experiments supporting the hygiene hypothesis using animal models of asthma. Exposure to the influenza virus early in life induces an NKT/regulatory T-cell-dependent protection against asthma later in life
6. F Grela A Aumeunier E Bardel, et al. 2011 R848 alleviates allergic inflammation by targeting invariant NKT cells to produce IFN-gamma J Immunol 186 284 290 21131420 1:CAS:528:DC%2BC3cXhs1ajtL3L
7. GW Scadding MH Shamji MR Jacobson, et al. 2010 Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergen-specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells Clin Exp Allergy 40 598 606 20184605 1:CAS:528:DC%2BC3cXltFGjurY%3D
8. E Shen L Lu C Wu 2008 TLR7/8 ligand, R-848, inhibits IgE synthesis by acting directly on B lymphocytes Scand J Immunol 67 560 568 18397197 1:CAS:528:DC%2BD1cXotFansLc%3D (Pubitemid 351677414)
9. M Roponen ST Yerkovich E Hollams, et al. 2010 Toll-like receptor 7 function is reduced in adolescents with asthma Eur Respir J 35 64 71 19643938 1:CAS:528:DC%2BC3cXislahtr8%3D
10. JN Kline TJ Waldschmidt TR Businga, et al. 1998 Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma J Immunol 160 2555 2559 9510150 1:CAS:528:DyaK1cXhvVWhtrw%3D (Pubitemid 28136702)
11. VV Jain K Kitagaki T Businga, et al. 2002 CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma J Allergy Clin Immunol 110 867 872 12464952 1:CAS:528:DC%2BD3sXlvFegug%3D%3D (Pubitemid 36005873)
12. VV Jain TR Businga K Kitagaki, et al. 2003 Mucosal immunotherapy with CpG oligodeoxynucleotides reverses a murine model of chronic asthma induced by repeated antigen exposure Am J Physiol Lung Cell Mol Physiol 285 L1137 L1146 12857672 1:CAS:528:DC%2BD3sXpt1Kitro%3D
13. JN Kline K Kitagaki TR Businga VV Jain 2002 Treatment of established asthma in a murine model using CpG oligodeoxynucleotides Am J Physiol Lung Cell Mol Physiol 283 L170 L179 12060574 1:CAS:528:DC%2BD38XlsVCqsr4%3D
14. JN Kline AM Krieg TJ Waldschmidt, et al. 1999 CpG oligodeoxynucleotides do not require TH1 cytokines to prevent eosinophilic airway inflammation in a murine model of asthma J Allergy Clin Immunol 104 1258 1264 10589010 1:CAS:528:DC%2BD3cXjt1yisQ%3D%3D (Pubitemid 30004989)
15. K Kitagaki VV Jain TR Businga I Hussain JN Kline 2002 Immunomodulatory effects of CpG oligodeoxynucleotides on established th2 responses Clin Diagn Lab Immunol 9 1260 1269 12414759 1:CAS:528:DC%2BD38XptFakt74%3D (Pubitemid 35283289)
16. T Hayashi L Beck C Rossetto, et al. 2004 Inhibition of experimental asthma by indoleamine 2, 3-dioxygenase J Clin Invest 114 270 279 15254594 1:CAS:528:DC%2BD2cXlvFWmsbs%3D (Pubitemid 39071632)
17. S Sel M Wegmann S Sel, et al. 2007 Immunomodulatory effects of viral TLR ligands on experimental asthma depend on the additive effects of IL-12 and IL-10 J Immunol 178 7805 7813 17548618 1:CAS:528:DC%2BD2sXmtVKnsrw%3D (Pubitemid 46898052)
18. A Vultaggio F Nencini S Pratesi, et al. 2011 The TLR7 ligand 9-benzyl-2-butoxy-8-hydroxy adenine inhibits IL-17 response by eliciting IL-10 and IL-10-inducing cytokines J Immunol 186 4707 4715 21389257 1:CAS:528:DC%2BC3MXkt1Gqsbo%3D TLR7 ligands can modulate Th17 responses via induction of IL-10
19. CF Yu WM Peng J Oldenburg, et al. 2010 Human plasmacytoid dendritic cells support Th17 cell effector function in response to TLR7 ligation J Immunol 184 1159 1167 20026744 1:CAS:528:DC%2BC3cXhtVGis7k%3D Contrasting results described in the paper by Vultaggio et al. [18•], this article shows that TLR7 activation may trigger Th17-type responses in humans
20. R Marino T Thuraisingam P Camateros, et al. 2011 Secretory leukocyte protease inhibitor plays an important role in the regulation of allergic asthma in mice J Immunol 186 4433 4442 21335488 1:CAS:528:DC%2BC3MXjvVKls70%3D
21. DE Fonseca JN Kline 2009 Use of CpG oligonucleotides in treatment of asthma and allergic disease Adv Drug Deliv Rev 61 256 262 19167442 1:CAS:528:DC%2BD1MXjtFKluro%3D
22. C Xirakia O Koltsida A Stavropoulos, et al. 2010 Toll-like receptor 7-triggered immune response in the lung mediates acute and long-lasting suppression of experimental asthma Am J Respir Crit Care Med 181 1207 1216 20224068 1:CAS:528:DC%2BC3cXhtFOhsrbE
23. MJ Duechs C Hahn E Benediktus, et al. 2011 TLR agonist mediated suppression of allergic responses is associated with increased innate inflammation in the airways Pulm Pharmacol Ther 24 203 214 21195789 1:CAS:528:DC%2BC3MXisFKjtbo%3D
24. K Kastenmüller U Wille-Reece RW Lindsay, et al. 2011 Protective T cell immunity in mice following protein-TLR7/8 agonist-conjugate immunization requires aggregation, type I IFN, and multiple DC subsets J Clin Invest 121 1782 1796 21540549 This paper describes optimal strategies for inducing TLR7-mediated protective T-cell immunity in mice
25. A Kurimoto K Hashimoto T Nakamura, et al. 2010 Synthesis and biological evaluation of 8-oxoadenine derivatives as toll-like receptor 7 agonists introducing the antedrug concept J Med Chem 53 2964 2972 20232824 1:CAS:528:DC%2BC3cXjt1CqtLs%3D
26. S Baenziger M Heikenwalder P Johansen, et al. 2009 Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology Blood 113 377 388 18824599 1:CAS:528: DC%2BD1MXptFSiug%3D%3D
27. K Hasegawa T Hayashi 2003 Synthetic CpG oligodeoxynucleotides accelerate the development of lupus nephritis during preactive phase in NZB x NZWF1 mice Lupus 12 838 845 14667100 1:CAS:528:DC%2BD3sXhtVSru7vL (Pubitemid 37463101)
28. HJ Anders V Vielhauer V Eis, et al. 2004 Activation of Toll-like receptor-9 induces progression of renal disease in MRL-Fas(lpr) mice FASEB J 18 534 536 14734643 1:CAS:528:DC%2BD2cXisVyhtb8%3D
29. DF Carpenter AD Steinberg PH Schur N Talal 1970 The pathogenesis of autoimmunity in New Zealand mice. II. Acceleration of glomerulonephritis by polyinosinic-polycytidylic acid Lab Invest 23 628 634 5312472 1:CAS:528:DyaE3MXnsV2jug%3D%3D
30. RD Pawar PS Patole D Zecher, et al. 2006 Toll-like receptor-7 modulates immune complex glomerulonephritis J Am Soc Nephrol 17 141 149 16280469 1:CAS:528:DC%2BD28XhtFyqu78%3D
31. P Pisitkun JA Deane MJ Difilippantonio, et al. 2006 Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication Science 312 1669 1672 16709748 1:CAS:528:DC%2BD28XlsFeqtb4%3D (Pubitemid 43902669)
32. IR Rifkin EA Leadbetter L Busconi, et al. 2005 Toll-like receptors, endogenous ligands, and systemic autoimmune disease Immunol Rev 204 27 42 15790348 1:CAS:528:DC%2BD2MXkslGnsrg%3D (Pubitemid 40460491)
33. L Ronnblom GV Alm 2001 An etiopathogenic role for the type I IFN system in SLE Trends Immunol 22 427 431 11473831 1:CAS:528:DC%2BD3MXltlyrtbY%3D (Pubitemid 32709976)
34. P Lenert 2006 Targeting Toll-like receptor signaling in plasmacytoid dendritic cells and autoreactive B cells as a therapy for lupus Arthritis Res Ther 8 R203
35. AM Krieg J Vollmer 2007 Toll-like receptors 7, 8, and 9: linking innate immunity to autoimmunity Immunol Rev 220 251 269 17979852 1:CAS:528: DC%2BD2sXhsVKgtrjM (Pubitemid 350045572)
36. NM Green A Marshak-Rothstein 2011 Toll-like receptor driven B cell activation in the induction of systemic autoimmunity Semin Immunol 23 106 112 21306913 1:CAS:528:DC%2BC3MXkt1eitrk%3D This is an excellent review clarifying the role of TLR receptors in autoimmune B-cell activation in systemic autoimmune disease
37. SE Ewald GM Barton 2011 Nucleic acid sensing Toll-like receptors in autoimmunity Curr Opin Immunol 23 3 9 21146971 1:CAS:528:DC%2BC3MXit1ygurk%3D
38. P Lenert 2005 Inhibitory oligodeoxynucleotides-therapeutic promise for systemic autoimmune diseases? Clin Exp Immunol 140 1 10 15762869 1:CAS:528:DC%2BD2MXjt12ltrc%3D (Pubitemid 40461067)
39. DM Klinman D Tross S Klaschik, et al. 2009 Therapeutic applications and mechanisms underlying the activity of immunosuppressive oligonucleotides Ann N Y Acad Sci 1175 80 88 19796080 1:CAS:528:DC%2BD1MXhtlGgu73N
40. MD Rosa JP Hendrick MR Lerner, et al. 1983 A mammalian tRNAHis-containing antigen is recognized by the polymyositis-specific antibody anti-Jo-1 Nucleic Acis Res 11 853 870 1:CAS:528:DyaL3sXht1eqtrg%3D
41. CM Lau C Broughton AS Tabor, et al. 2005 RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement J Exp Med 202 1171 1177 16260486 1:CAS:528:DC%2BD2MXht1Sntr7F (Pubitemid 41586947)
42. EA Leadbetter IR Rifkin AM Hohlbaum, et al. 2002 Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors Nature 416 603 607 11948342 1:CAS:528:DC%2BD38XjtFahur8%3D (Pubitemid 34406754)
43. L Busconi JW Bauer JR Tumang, et al. 2007 Functional outcome of B cell activation by chromatin immune complex engagement of the B cell receptor and TLR9 J Immunol 179 7397 7405 18025183 1:CAS:528:DC%2BD2sXhtlajt7zI
44. O Demaria PP Pagni S Traub, et al. 2010 TLR8 deficiency leads to autoimmunity in mice J Clin Invest 120 3651 3662 20811154 1:CAS:528: DC%2BC3cXht1GgtLfF This was the first paper to demonstrate that the lack of single-stranded RNA sensor, TLR8, in healthy mice results in TLR7-mediated immune hyperactivation and autoimmune kidney injury
45. P Lenert R Brummel EH Field RF Ashman 2005 TLR-9 activation of marginal zone B cells in lupus mice regulates immunity through increased IL-10 production J Clin Immunol 25 29 40 15742155 1:CAS:528:DC%2BD2MXhslGnsLY%3D (Pubitemid 40386176)
46. X Wu SL Peng 2006 Toll-like receptor 9 signaling protects against murine lupus Arthritis Rheum 54 336 342 16385525 1:CAS:528:DC%2BD28XhsVensbk%3D (Pubitemid 43122217)
47. SR Christensen J Shupe K Nickerson, et al. 2006 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 16973389 1:CAS:528:DC%2BD28XhtVOjtLzN (Pubitemid 44354217)
48. H Hemmi O Takeuchi T Kawai, et al. 2000 A toll-like receptor recognizes bacterial DNA Nature 408 740 745 11130078 1:CAS:528:DC%2BD3cXptVCqsL0%3D (Pubitemid 32015992)
49. ML Santiago-Raber I Dunand-Sauthier T Wu, et al. 2010 Critical role of TLR7 in the acceleration of systemic lupus erythematosus in TLR9-deficient mice J Autoimmun 34 339 348 19944565 1:CAS:528:DC%2BC3cXltF2ms7g%3D
50. KM Nickerson SR Christensen J Shupe, et al. 2010 TLR9 regulates TLR7- and MyD88-dependent autoantibody production and disease in a murine model of lupus J Immunol 184 1840 1848 20089701 1:CAS:528:DC%2BC3cXhsVGlur8%3D This article provided evidence that TLR9 controlled TLR7-mediated autoimmune injury in a murine model of spontaneous lupus
51. J Vollmer S Tluk C Schmitz, et al. 2005 Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8 J Exp Med 202 1575 1585 16330816 1:CAS:528:DC%2BD2MXhtlSqtLbJ (Pubitemid 41746603)
52. RM Clancy D Alvarez E Komissarova, et al. 2010 Ro60-associated single-stranded RNA links inflammation with fetal cardiac fibrosis via ligation of TLRs: a novel pathway to autoimmune-associated heart block J Immunol 184 2148 2155 20089705 1:CAS:528:DC%2BC3cXhsVGks78%3D
53. A Sheriff US Gaipl RE Voll, et al. 2004 Apoptosis and systemic lupus erythematosus Rheum Dis Clin North Am 30 505 527 15261339 (Pubitemid 38916999)
54. M Radic T Marion M Monestier 2004 Nucleosomes are exposed at the cell surface in apoptosis J Immunol 172 1317 1330
55. LA Casciola-Rosen G Anhalt A Rosen 1994 Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes J Exp Med 179 1317 1330 7511686 1:CAS:528: DyaK2cXhs1Wms7Y%3D (Pubitemid 24091790)
56. W Emlen J Niebur R Kadera 1994 Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus J Immunol 152 3685 3692 8144943 1:STN:280:DyaK2c7psVWgsg%3D%3D (Pubitemid 24098067)
57. Y Ren J Tang MY Mok, et al. 2003 Increased apoptotic neutrophils and macrophages and impaired macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosus Arthritis Rheum 48 2888 2897 14558095 (Pubitemid 37280618)
58. A Hakkim BG Furnrohr K Amann, et al. 2010 Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis Proc Natl Acad Sci USA 107 9813 9818 20439745 1:CAS:528:DC%2BC3cXntFGqt74%3D
59. P Lenert K Yasuda L Busconi, et al. 2009 DNA-like class R inhibitory oligonucleotides (INH-ODNs) preferentially block autoantigen-induced B-cell and dendritic cell activation in vitro and autoantibody production in lupus-prone MRL-Faslpr/lpr mice in vivo Arthritis Res Ther 11 R79 19476613 This article highlights cell-type-dependent differences in the inhibitory potential of palindromic versus linear INH-ODNs and the effect of B-cell receptor engagement on overcoming these differences in autoreactive B cells from lupus mice
60. PS Patole D Zecher RD Pawar, et al. 2005 G-rich DNA suppresses systemic lupus JASN 16 3273 3280 16176997 1:CAS:528:DC%2BD2MXht1CnsrzL (Pubitemid 46187549)
61. L Dong S Ito KJ Ishii DM Klinman 2005 Suppressive oligodeoxynucleotides delay the onset of glomerulonephritis and prolong survival in lupus-prone NZB x NZW mice Arthritis Rheum 52 651 658 15692999 1:CAS:528:DC%2BD2MXit1Gjtbc%3D (Pubitemid 40216332)
62. FJ Barrat T Meeker JH Chan, et al. 2007 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 18034431 1:CAS:528:DC%2BD1cXhsVegsw%3D%3D
63. RD Pawar A Ramanjaneyulu OP Kulkarni, et al. 2007 Inhibition of Toll-like receptor-7 (TLR-7) or TLR-7 plus TLR-9 attenuates glomerulonephritis and lung injury in experimental lupus JASN 18 1721 1731 17460144 1:CAS:528: DC%2BD2sXnt1Squ78%3D (Pubitemid 46870309)
64. KL Graham LY Lee JP Higgins, et al. 2010 Treatment with a Toll-like receptor inhibitory GpG oligonucleotide delays and attenuates lupus nephritis in NZB/W mice Autoimmunity 43 140 155 19845477 1:CAS:528:DC%2BC3cXisFSitrs%3D
65. C Guiducci C Tripodo M Gong, et al. 2010 Autoimmune skin inflammation is dependent on plasmacytoid dendritic cell activation by nucleic acids via TLR7 and TLR9 J Exp Med 207 2931 2942 21115693 1:CAS:528:DC%2BC3cXhs1artbzJ This was the first publication to establish the role of TLR7 and TLR9 in a novel animal model of autoimmune skin disease
66. JP Messina GS Gilkeson DS Pisetsky 1991 Stimulation of in vitro murine lymphocyte proliferation by bacterial DNA J Immunol 147 1759 1764 1890302 1:CAS:528:DyaK3MXmsFCju7c%3D
67. AM Krieg AK Yi S Matson, et al. 1995 CpG motifs in bacterial DNA trigger direct B-cell activation Nature 374 546 549 7700380 1:CAS:528:DyaK2MXkvVKqtr8%3D
68. MD Halpern DS Pisetsky 1995 In vitro inhibition of murine IFN gamma production by phosphorothioate deoxyguanosine oligomers Immunopharmacology 29 47 52 7768671 1:CAS:528:DyaK2MXjsFamtr8%3D
69. DS Pisetsky CF Reich 2000 Inhibition of murine macrophage IL-12 production by natural and synthetic DNA Clin Immunol 96 198 204 10964537 1:CAS:528:DC%2BD3cXntFSiurY%3D
70. FG Zhu CF Reich DS Pisetsky 2002 Inhibition of murine dendritic cell activation by synthetic phosphorothioate oligodeoxynucleotides J Leukoc Biol 72 1154 1163 12488497 1:CAS:528:DC%2BD3sXhtF2mug%3D%3D (Pubitemid 36008886)
71. AM Krieg T Wu R Weeratna, et al. 1998 Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs PNAS 95 12631 12636 9770537 1:CAS:528:DyaK1cXmsl2qur8%3D (Pubitemid 28483816)
72. H Hacker H Mischak T Miethke, et al. 1998 CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation EMBO J 17 6230 6240 9799232 1:CAS:528:DyaK1cXnsVKht7o%3D (Pubitemid 28497796)
73. P Ahmad-Nejad H Hacker M Rutz, et al. 2002 Bacterial CpG-DNA and lipolysaccharides activate Toll-like receptors at distinct cellular compartments Eur J Immunol 32 1958 1968 12115616 1:CAS:528:DC%2BD38XlsFajurg%3D (Pubitemid 34814552)
74. E Latz A Schoenemeyer A Visintin, et al. 2004 TLR9 signals after translocating from the ER to CpG DNA in the lysosome Nat Immunol 5 190 198 14716310 1:CAS:528:DC%2BD2cXntFWnug%3D%3D (Pubitemid 38208361)
75. Y-M Kim MM Brinkmann M-E Paquet HL Ploegh 2008 UNC93B1 delivers nucleotide-sensing Toll-like receptors to endolysosomes Nature 452 234 238 18305481 1:CAS:528:DC%2BD1cXjt1Gnu7w%3D (Pubitemid 351380247)
76. DH Kono MK Haraldsson BR Lawson, et al. 2009 Endosomal TLR signaling is required for anti-nucleic acid and rheumatoid factor autoantibodies in lupus PNAS 106 12061 12066 19574451 1:CAS:528:DC%2BD1MXps1anu74%3D
77. K Tabeta K Hoebe EM Janssen, et al. 2006 The Unc93b1 mutation 3 d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9 Nature Immunol 7 156 164 1:CAS:528:DC%2BD28Xlt1ersA%3D%3D (Pubitemid 43135881)
78. SE Ewald BL Lee L Lau, et al. 2008 The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor Nature 456 658 662 18820679 1:CAS:528:DC%2BD1cXhsVGlur%2FL
79. B Park MM Brinkmann E Spooner, et al. 2008 Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9 Nat Immunol 9 1407 1414 18931679 1:CAS:528:DC%2BD1cXhtlOjsb3J
80. FE Sepulveda S Maschalidi R Colisson, et al. 2009 Critical role for asparagine endopeptidase in endocytic Toll-like receptor signaling in dendritic cells Immunity 31 737 748 19879164 1:CAS:528:DC%2BD1MXhsFylsbjN In dendritic cells, asparagine endopeptidase may play a critical role in TLR9 processing within endosomes
81. SE Ewald A Engel J Lee, et al. 2011 Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase J Exp Med 20 643 651 This article presents evidence for a stepwise TLR3, TRL7, and TLR9 processing mediated by cathepsins and asparagine endopeptidase in different cell types
82. P Lenert W Rasmussen RF Ashman ZK Ballas 2003 Structural characterization of the inhibitory DNA motif for the type A[D]-CpG-induced cytokine secretion and NK-cell lytic activity in mouse spleen cells DNA Cell Biol 22 621 631 14611683 1:CAS:528:DC%2BD3sXotlyqs7g%3D (Pubitemid 37357732)
83. RF Ashman JA Goeken J Drahos P Lenert 2005 Sequence requirements for oligodeoxyribonucleotide inhibitory activity Int Immunol 17 411 420 15746247 1:CAS:528:DC%2BD2MXivFWit74%3D (Pubitemid 40568116)
84. LL Stunz P Lenert D Peckham, et al. 2002 Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells Eur J Immunol 32 1212 1222 11981808 1:CAS:528:DC%2BD38XjvFKjsrs%3D (Pubitemid 34546248)
85. RF Ashman P Lenert 2007 Structural requirements and applications of inhibitory oligodeoxyribonucleotides Immunol Res 39 4 14 17917051 1:CAS:528:DC%2BD2sXhtlertbjF (Pubitemid 47574896)
86. RF Ashman JA Goeken E Latz P Lenert 2011 Optimal oligonucleotide sequences for TLR9 inhibitory activity in human cells: lack of correlation with TLR9 binding Int Immunol 23 203 214 21393636 1:CAS:528:DC%2BC3MXjtFWgurc%3D This was the first paper to fully elaborate requirements for TLR9 inhibition in human cells. Furthermore, while studying the receptor-ligand interaction, the authors observed that direct binding to full-length TLR9 failed to explain differences in biologic activities of INH-ODNs
87. P Lenert L Stunz AK Yi, et al. 2001 CpG stimulation of primary mouse B cells is blocked by inhibitory oligodeoxyribonucleotides at a site proximal to NF-kappaB activation Antisense Nuc Acid Drug Dev 11 247 256 1:CAS:528: DC%2BD3MXmslCks7g%3D (Pubitemid 32852883)
88. K Stacey GR Young F Clark, et al. 2003 The molecular basis for the lack of immunostimulatory activity of vertebrate DNA J Immunol 170 3614 3620 12646625 1:CAS:528:DC%2BD3sXitFKlt7o%3D (Pubitemid 36359230)
89. RA Zeuner D Verthelyi M Gursel, et al. 2003 Influence of stimulatory and suppressive DNA motifs on host susceptibility to inflammatory arthritis Arthritis Rheum 48 1701 1707 12794839 1:CAS:528:DC%2BD3sXltlSgu7g%3D (Pubitemid 36682379)
90. M Peter K Bode GB Lipford, et al. 2008 Characterization of suppressive oligodeoxynucleotides that inhibit Toll-like receptor-9-mediated activation of innate immunity Immunology 123 118 128 17961163 1:CAS:528:DC%2BD1cXnsFWjtA%3D%3D (Pubitemid 350256002)
91. O Duramad KL Fearon B Chang, et al. 2005 Inhibitors of TLR-9 act on multiple cell subsets in mouse and man in vitro and prevent death in vivo from systemic inflammation J Immunol 174 5193 5200 15843514 1:CAS:528: DC%2BD2MXjsVertrw%3D (Pubitemid 40593156)
92. PS Lenert 2010 Classification, mechanisms of action, and therapeutic applications of inhibitory oligonucleotides for Toll-like receptors (TLR) 7 and 9 Mediators Inflamm 2010 986596 20490286 This article provides classification of INH-ODNs based on their ability to make linear structures, dimers/hairpins, or G4 stacks. Also included is a description of optimal sequence requirements for TLR7 and TLR9 inhibition in humans and rodents
93. P Lenert 2010 Nucleic acid sensing receptors in systemic lupus erythematosus: development of novel DNA- and/or RNA-like analogues for treating lupus Clin Exp Immunol 161 208 222 20456414 1:CAS:528:DC%2BC3cXhtV2itLvO
94. T Haas J Metzger F Schmitz, et al. 2008 The DNA sugar backbone 2' deoxyribose determines Toll-like receptor 9 activation Immunity 28 315 323 18342006 1:CAS:528:DC%2BD1cXjvFeksLw%3D (Pubitemid 351335308)
95. A Trieu TL Roberts JA Dunn, et al. 2006 DNA motifs suppressing TLR9 responses Critical Rev Immunol 26 527 544 1:CAS:528:DC%2BD2sXjs1Gktb8%3D
96. I Gursel M Gursel H Yamada, et al. 2003 Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation J Immunol 171 1393 1400 12874230 1:CAS:528:DC%2BD3sXlsFyltr0%3D (Pubitemid 36900072)
97. T Sato T Shimosato WG Alvord DM Klinman 2008 Suppressive oligodeoxynucleotides inhibit silica-induced pulmonary inflammation J Immunol 180 7648 7654 18490767 1:CAS:528:DC%2BD1cXmtVams7k%3D
98. H Shirota I Gursel M Gursel DM Klinman 2005 Suppressive oligodeoxynucleotides protect mice from lethal endotoxic shock J Immunol 174 4579 4583 15814679 1:CAS:528:DC%2BD2MXivFKit74%3D
99. H Ikeuchi T Kinjo DM Klinman 2011 Effect of suppressive oligodeoxynucleotides on the development of inflammation-induced papillomas Cancer Prev Res (Phila) 4 752 757 1:CAS:528:DC%2BC3MXnslektbw%3D
100. E Latz A Verma A Visintin, et al. 2007 Ligand-induced conformational changes allosterically activate Toll-like receptor 9 Nat Immunol 8 772 779 17572678 1:CAS:528:DC%2BD2sXms1Wgur4%3D (Pubitemid 46965353)
101. RF Ashman JA Goeken PS Lenert 2011 Aggregation and secondary loop structure of oligonucleotides do not determine their ability to inhibit TLR9 Int Immunopharmacol 11 1032 1037 21376154 1:CAS:528:DC%2BC3MXptVSqsrk%3D
102. A Kuznik M Bencina U Svajger, et al. 2011 Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines J Immunol 186 4794 4804 21398612 1:CAS:528:DC%2BC3MXkt1Gqtr0%3D This was the first publication to show that antimalarial drugs block TLR activation by directly binding to nucleic acids, not, as previously believed, through the inhibition of endosomal acidification
103. DE Macfarlane L Manzel 1998 Antagonism of immunostimulatory CpG-oligodeoxynucleotides by quinacrine, chloroquine, and structurally related compounds J Immunol 160 1122 1131 9570525 1:CAS:528:DyaK1cXns1Ohsg%3D%3D (Pubitemid 28093406)
104. JA Goeken T Layer S Fleenor, et al. 2010 B-cell receptor for antigen modulates B-cell responses to complex TLR9 agonists and antagonists: implications for systemic lupus erythematosus Lupus 19 1290 12301 20605877 1:CAS:528:DC%2BC3cXhsVWjsr7J
105. TL Roberts ML Turner JA Dunn, et al. 2011 B cells do not take up bacterial DNA: an essential role for antigen in exposure of DNA to toll-like receptor-9 Immunol Cell Biol 89 517 525 20921967 1:CAS:528:DC%2BC3MXls1Khu7o%3D
106. AM Avalos E Latz B Mousseau, et al. 2009 Differential cytokine production and bystander activation of autoreactive B cells in response to CpG-A and CpG-B oligonucleotides J Immunol 183 6262 6268 19864612 1:CAS:528:DC%2BD1MXhtlKhsbnK
107. FJ Barrat T Meeker J Gregorio, et al. 2005 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 16230478 1:CAS:528:DC%2BD2MXhtFelu7vO (Pubitemid 41464506)
108. A Chaturvedi D Dorwald SK Pierce 2008 The B cell receptor governs the subcellular location of Toll-like receptor 9 leading to hyperresponses to DNA-containing antigens Immunity 28 799 809 18513998 1:CAS:528: DC%2BD1cXnsF2gu7s%3D
109. H Hacker RM Vabulas O Takeuchi, et al. 2000 Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6 J Exp Med 192 595 600 10952730 1:CAS:528:DC%2BD3cXlvFemsLk%3D (Pubitemid 30666261)
110. M Muzio G Natoli S Saccani, et al. 1998 The human Toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6) J Exp Med 187 2097 2101 9625770 1:CAS:528:DyaK1cXktVemsbk%3D (Pubitemid 28285580)
111. M Rutz J Metzger T Gellert, et al. 2004 Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner Eur J Immunol 34 2541 2550 15307186 1:CAS:528:DC%2BD2cXns1yntr8%3D (Pubitemid 39302811)
112. •• Avalos AM, Ploegh HL: Competition by inhibitory oligonucleotides prevents binding of CpG to C-terminal TLR9. Eur J Immunol 2011, doi: 10.1002/eji.201141563. CpG-ODNs and INH-ODNs, but not control ODNs, preferentially compete for binding to the C-terminal TLR9 fragment.
113. ME Peter AV Kubarenko AN Weber AH Dalpke 2009 Identification of an N-terminal recognition site in TLR9 that contributes to CpG-DNA-mediated receptor activation J Immunol 182 7690 7697 19494293 1:CAS:528: DC%2BD1MXmslCnsbg%3D
114. M Jurk A Kritzler B Schulte, et al. 2006 Modulating responsiveness of human TLR7 and 8 to small molecule ligands with T-rich phosphorothioate oligodeoxynucleotides Eur J Immunol 36 1815 1826 16783850 1:CAS:528: DC%2BD28XnslOmsr8%3D (Pubitemid 44089048)
115. KK Gorden X Qiu JJ Batiste, et al. 2006 Oligodeoxynucleotides differentially modulate activation of TLR7 and TLR8 by imidazoquinolines J Immunol 177 8164 8170 17114492 1:CAS:528:DC%2BD28Xht1WrsLnN (Pubitemid 44846336)
116. T Layer A Steele JA Goeken, et al. 2011 Engagement of the B cell receptor for antigen differentially affects B cell responses to Toll-like receptor-7 agonists and antagonists in BXSB mice Clin Exp Immunol 163 392 403 21235537 1:CAS:528:DC%2BC3MXjsFOnsLY%3D In contrast to the TLR9/B-cell receptor cross-talk, which enhances the potency of palindromic INH-ODNs for TLR9 inhibition, TLR7/B-cell receptor co-activation may restrict the ability of INH-ODNs to block TLR7-dependent activation events, with practical implications for future strategies in managing lupus