toll like receptor 9

Summary

Summary: A pattern recognition receptor that binds unmethylated CPG CLUSTERS. It mediates cellular responses to bacterial pathogens by distinguishing between self and bacterial DNA.

Top Publications

  1. Wuest T, Austin B, Uematsu S, Thapa M, Akira S, Carr D. Intact TRL 9 and type I interferon signaling pathways are required to augment HSV-1 induced corneal CXCL9 and CXCL10. J Neuroimmunol. 2006;179:46-52 pubmed
    ..This is the first report that shows enhanced CXCL10 expression following neurotropic viral replication requires both intact TLR 9 and type I interferon signaling pathways. ..
  2. Carpenter E, Mick R, Ruter J, Vonderheide R. Activation of human B cells by the agonist CD40 antibody CP-870,893 and augmentation with simultaneous toll-like receptor 9 stimulation. J Transl Med. 2009;7:93 pubmed publisher
    ..subsets from peripheral blood were stimulated in vitro with CP-870,893, in the presence or absence of the toll like receptor 9 (TLR9) ligand CpG oligodeoxynucleotide (ODN)...
  3. Trieu A, Bokil N, Dunn J, Roberts T, Xu D, Liew F, et al. TLR9-independent effects of inhibitory oligonucleotides on macrophage responses to S. typhimurium. Immunol Cell Biol. 2009;87:218-25 pubmed publisher
  4. Xu C, Zhang W, Pan H, Li X, Xu J, Ye D. Association study of a single nucleotide polymorphism in the exon 2 region of toll-like receptor 9 (TLR9) gene with susceptibility to systemic lupus erythematosus among Chinese. Mol Biol Rep. 2009;36:2245-8 pubmed publisher
    ..004, P = 0.045067). Our study suggests that a single nucleotide polymorphism (rs352140) in the exon 2 region of TLR9 gene may be a susceptibility factor for SLE in Chinese population. ..
  5. Lee J, Cho M, Kim J, Moon Y, Oh H, Kim G, et al. Interleukin 17 (IL-17) increases the expression of Toll-like receptor-2, 4, and 9 by increasing IL-1beta and IL-6 production in autoimmune arthritis. J Rheumatol. 2009;36:684-92 pubmed publisher
    ..These results imply that the IL-17-induced increase in expression of TLR-2, 4, and 9, and IL-1beta and IL-6 production are involved in the IL-17-induced aggravation of arthritis. ..
  6. BOOTH J, Griebel P, Babiuk L, Mutwiri G. A novel regulatory B-cell population in sheep Peyer's patches spontaneously secretes IL-10 and downregulates TLR9-induced IFNalpha responses. Mucosal Immunol. 2009;2:265-75 pubmed publisher
    ..These IL-10-secreting PP B cells may represent a novel subset of the recently proposed regulatory B cells (B(regs)) in the intestine. ..
  7. Di Paolo N, Miao E, Iwakura Y, Murali Krishna K, Aderem A, Flavell R, et al. Virus binding to a plasma membrane receptor triggers interleukin-1 alpha-mediated proinflammatory macrophage response in vivo. Immunity. 2009;31:110-21 pubmed publisher
    ..Thus, these data identify IL-1 alpha-IL-1RI as a key pathway allowing for the activation of proinflammatory responses to the virus, independently of its genomic nucleic acid recognition. ..
  8. Sepulveda F, Maschalidi S, Colisson R, Heslop L, Ghirelli C, Sakka E, et al. Critical role for asparagine endopeptidase in endocytic Toll-like receptor signaling in dendritic cells. Immunity. 2009;31:737-48 pubmed publisher
    ..When expressed in AEP-deficient DCs, the 72 kDa proteolytic fragment restored TLR9 signaling. Thus, our results identify an endocytic protease playing a critical role in TLR processing and signaling in DCs. ..
  9. Avalos A, Kiefer K, Tian J, Christensen S, Shlomchik M, Coyle A, et al. RAGE-independent autoreactive B cell activation in response to chromatin and HMGB1/DNA immune complexes. Autoimmunity. 2010;43:103-10 pubmed publisher
    ..We found that spontaneous and defined DNA ICs activated RAGE+ and RAGE(- ) AM14 B cells to a comparable extent. These results suggest that HMGB1 promotes B cell responses to endogenous TLR9 ligands through a RAGE-independent mechanism. ..

More Information

Publications62

  1. Lepelletier Y, Zollinger R, Ghirelli C, Raynaud F, Hadj Slimane R, Cappuccio A, et al. Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid predendritic cells (pDCs). Blood. 2010;116:3389-97 pubmed publisher
    ..Our results demonstrate a novel property of the TLR pathway in regulating the interface between GC and innate immunity and reveal a previously undescribed mechanism of GC resistance. ..
  2. Alizadeh D, Zhang L, Brown C, Farrukh O, Jensen M, Badie B. Induction of anti-glioma natural killer cell response following multiple low-dose intracerebral CpG therapy. Clin Cancer Res. 2010;16:3399-408 pubmed publisher
    ..These findings suggest that multiple low-dose intratumoral injections of CpG-ODN can eradicate intracranial gliomas possibly through mechanisms involving NK-mediated effector function. ..
  3. Wong R, Smith K, Tam V, Pagarigan R, Meisenburg B, Quach A, et al. TLR-9 signaling and TCR stimulation co-regulate CD8(+) T cell-associated PD-1 expression. Immunol Lett. 2009;127:60-7 pubmed publisher
    ..These data hint at strategies to elicit PD-1(low) CD8(+) T cells using TLR-9 ligand adjuvants, and also shed light on the PD-1-regulated homeostasis of CD8(+) T cells. ..
  4. Tang J, Yang Y, Sun L. [Expression of blood Toll-like receptors and cytokines in children with recurrent herpes simplex]. Zhongguo Dang Dai Er Ke Za Zhi. 2009;11:722-4 pubmed
    ..The production and release of IL-6 and IL-10 might be mediated by TLR2 and TLR9. ..
  5. Long A. Monoclonal antibodies and other biologic agents in the treatment of asthma. MAbs. 2009;1:237-46 pubmed
    ..An improved understanding of the heterogeneity of asthma should allow for specific targeting of different disease phenotypes specific therapies including immunomodulators. ..
  6. Olbert P, Schrader A, Simon C, Dalpke A, Barth P, Hofmann R, et al. In vitro and in vivo effects of CpG-Oligodeoxynucleotides (CpG-ODN) on murine transitional cell carcinoma and on the native murine urinary bladder wall. Anticancer Res. 2009;29:2067-76 pubmed
    ..The mechanisms of action appear to be mediated immunologically, There was no direct effect of CpG-ODN on the tumor cells in this model. ..
  7. Morrison V, Barr T, Brown S, Gray D. TLR-mediated loss of CD62L focuses B cell traffic to the spleen during Salmonella typhimurium infection. J Immunol. 2010;185:2737-46 pubmed publisher
    ..We propose that wholesale TLR-mediated changes to B cell migration influence the development of immunity to pathogens carrying appropriate ligands. ..
  8. Nørgaard N, Holien T, Jonsson S, Hella H, Espevik T, Sundan A, et al. CpG-oligodeoxynucleotide inhibits Smad-dependent bone morphogenetic protein signaling: effects on myeloma cell apoptosis and in vitro osteoblastogenesis. J Immunol. 2010;185:3131-9 pubmed publisher
    ..In conclusion, our results demonstrate that PTO-CpG-ODN inhibits BMP-signaling, and thus might provoke unwanted TLR9-independent side effects in patients. ..
  9. Avalos A, Uccellini M, Lenert P, Viglianti G, Marshak Rothstein A. Fc?RIIB regulation of BCR/TLR-dependent autoreactive B-cell responses. Eur J Immunol. 2010;40:2692-8 pubmed publisher
    ..These results demonstrate that Fc?RIIB can effectively modulate both BCR/TLR9 and BCR/TLR7 endosomal-dependent activation of autoreactive B cells. ..
  10. Richter C, Juan M, Will J, Brandes R, Kalinke U, Akira S, et al. Ncf1 provides a reactive oxygen species-independent negative feedback regulation of TLR9-induced IL-12p70 in murine dendritic cells. J Immunol. 2009;182:4183-91 pubmed publisher
    ..These data suggest for the first time an important role for Ncf1 in the fine tuning of the TLR9/MyD88 pathway in vitro and in vivo that is independent of its role as an activator of NOX2. ..
  11. Campino S, Forton J, Auburn S, Fry A, Diakite M, Richardson A, et al. TLR9 polymorphisms in African populations: no association with severe malaria, but evidence of cis-variants acting on gene expression. Malar J. 2009;8:44 pubmed publisher
    ..This report also shows that TLR9 expression is potentially modulated through cis-regulatory variants, which may lead to differential inflammatory responses to infection between individuals. ..
  12. Chockalingam A, Brooks J, Cameron J, Blum L, Leifer C. TLR9 traffics through the Golgi complex to localize to endolysosomes and respond to CpG DNA. Immunol Cell Biol. 2009;87:209-17 pubmed publisher
    ..Together, these data support a model where TLR9 uses traditional secretory pathways and does not bypass the Golgi complex. ..
  13. Miura K, Kodama Y, Inokuchi S, Schnabl B, Aoyama T, Ohnishi H, et al. Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1beta in mice. Gastroenterology. 2010;139:323-34.e7 pubmed publisher
    ..In a mouse model of NASH, TLR9 signaling induces production of IL-1beta by Kupffer cells, leading to steatosis, inflammation, and fibrosis. ..
  14. Zhang X, Munegowda M, Yuan J, Wei Y, Xiang J. Optimal TLR9 signal converts tolerogenic CD4-8- DCs into immunogenic ones capable of stimulating antitumor immunity via activating CD4+ Th1/Th17 and NK cell responses. J Leukoc Biol. 2010;88:393-403 pubmed publisher
  15. Kat I, Makdasi E, Fischel R, Eilat D. B-cell anergy is maintained in anti-DNA transgenic NZB/NZW mice. Int Immunol. 2010;22:101-11 pubmed publisher
    ..We conclude that low-affinity anergic B cells are unlikely to serve as precursors for the high-affinity autoreactive B cells that give rise to pathogenic anti-DNA auto-antibodies in SLE. ..
  16. Iha K, Omatsu T, Watanabe S, Ueda N, Taniguchi S, Fujii H, et al. Molecular cloning and expression analysis of bat toll-like receptors 3, 7 and 9. J Vet Med Sci. 2010;72:217-20 pubmed
    ..In addition, the expression profiles of each TLR in main organs were analyzed. Expression of TLR3 was highest in the liver, whereas the expressions of TLR7 and TLR9 were highest in the spleen. ..
  17. Avalos A, Latz E, Mousseau B, Christensen S, Shlomchik M, Lund F, et al. Differential cytokine production and bystander activation of autoreactive B cells in response to CpG-A and CpG-B oligonucleotides. J Immunol. 2009;183:6262-8 pubmed publisher
    ..These data identify direct and indirect mechanisms by which BCR engagement facilitates access of exogenous ligands to TLR9-associated compartments and subsequent B cell activation. ..
  18. Kim J, Lee I, Son M, Kim K. Effects of orally administered Actinidia arguta (Hardy Kiwi) fruit extract on 2-chloro-1,3,5-trinitrobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice. J Med Food. 2009;12:1004-15 pubmed publisher
  19. Liao W, Chen R, Lin H, Liu Y, Chen W, Tsai Y, et al. Toll-like receptor gene polymorphisms are associated with susceptibility to Graves' ophthalmopathy in Taiwan males. BMC Med Genet. 2010;11:154 pubmed publisher
    ..09-3.73) than those not carrying the GA haplotype. The present data suggest that TLR-9 gene polymorphisms were significantly associated with increased susceptibility of ophthalmopathy in male GD patients. ..
  20. Frank S, Copanaki E, Burbach G, Müller U, Deller T. Differential regulation of toll-like receptor mRNAs in amyloid plaque-associated brain tissue of aged APP23 transgenic mice. Neurosci Lett. 2009;453:41-4 pubmed publisher
    ..Since TLR-upregulation is restricted to plaques, modifying TLR-signaling may be a promising therapeutic strategy for plaque removal. ..
  21. Imajo N, Kurihara D, Fukuishi N, Inukai A, Matsushita S, Noda S, et al. Lipoteichoic acid improves the capability of mast cells in the host defense system against bacteria. Inflamm Res. 2009;58:797-807 pubmed publisher
    ..LTA increases the capability of the MC as a sentinel in the host immune response, and some bacterial components direct human MC function towards innate immunity after pathogen infection. ..
  22. Hughes T, Langer S, Virtanen S, Chavez R, Watkins L, Milligan E, et al. Immunogenicity of intrathecal plasmid gene delivery: cytokine release and effects on transgene expression. J Gene Med. 2009;11:782-90 pubmed publisher
    ..Furthermore, the development of methods to prevent loss of plasmid via CSF flow out of the central nervous system through the injection hole and/or natural outflow routes may increase intrathecal plasmid gene delivery efficacy. ..
  23. Sun R, Sun L, Bao M, Zhang Y, Wang L, Wu X, et al. A human microsatellite DNA-mimicking oligodeoxynucleotide with CCT repeats negatively regulates TLR7/9-mediated innate immune responses via selected TLR pathways. Clin Immunol. 2010;134:262-76 pubmed publisher
    ..The data suggest that SAT05f could be developed as a candidate medicament for the treatment of TLR7/9 activation-associated diseases by inhibiting TLR7/9 signaling pathways. ..
  24. Keestra A, de Zoete M, Bouwman L, van Putten J. Chicken TLR21 is an innate CpG DNA receptor distinct from mammalian TLR9. J Immunol. 2010;185:460-7 pubmed publisher
    ..The analogous localization and function of the phylogenetically only distantly related chTLR21 and mammalian TLR9 suggest that during evolution different classes of TLRs have emerged that recognize the same type of ligands. ..
  25. Okuya K, Tamura Y, Saito K, Kutomi G, Torigoe T, Hirata K, et al. Spatiotemporal regulation of heat shock protein 90-chaperoned self-DNA and CpG-oligodeoxynucleotide for type I IFN induction via targeting to static early endosome. J Immunol. 2010;184:7092-9 pubmed publisher
    ..Thus, extracellular Hsp90 converts inert self-DNA/CpG-ODNs into a potent trigger of IFN-alpha production via spatiotemporal regulation. ..
  26. Yoshida H, Nishikawa M, Yasuda S, Mizuno Y, Toyota H, Kiyota T, et al. TLR9-dependent systemic interferon-beta production by intravenous injection of plasmid DNA/cationic liposome complex in mice. J Gene Med. 2009;11:708-17 pubmed publisher
  27. Liao A, Salajegheh M, Morehouse C, Nazareno R, Jubin R, Jallal B, et al. Human plasmacytoid dendritic cell accumulation amplifies their type 1 interferon production. Clin Immunol. 2010;136:130-8 pubmed publisher
    ..The role of the IFNAR-dependent mechanism of interferon production by human pDCs is greater than previously suggested. IFNAR blockade has potential for diminishing type 1 interferon production by all human cells. ..
  28. Quan T, Roman R, Rudenga B, Holers V, Craft J. Epstein-Barr virus promotes interferon-alpha production by plasmacytoid dendritic cells. Arthritis Rheum. 2010;62:1693-701 pubmed publisher
    ..Our results suggest that elevated levels of IFNalpha found in SLE patients may be a result of aberrantly controlled chronic viral infection. ..
  29. Fang J, Fang D, Silver P, Wen F, Li B, Ren X, et al. The role of TLR2, TRL3, TRL4, and TRL9 signaling in the pathogenesis of autoimmune disease in a retinal autoimmunity model. Invest Ophthalmol Vis Sci. 2010;51:3092-9 pubmed publisher
    ..These results suggest that signaling of TLR2, TRL3, TRL4, and TRL9 is highly redundant in the adjuvant effect needed to induce EAU and that diverse microbial infections may contribute to the pathogenesis of diseases such as uveitis. ..
  30. Yoshizaki M, Tazawa A, Kasumi E, Sasawatari S, Itoh K, Dohi T, et al. Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q. Blood. 2009;114:1518-27 pubmed publisher
    ..Our data highlight a novel mechanism by which TLR9 signaling is controlled through the spatiotemporal regulation of membrane trafficking by the immunoreceptor tyrosine-based inhibitory motif-bearing receptor Ly49Q. ..
  31. Ermakov A, Konkova M, Kostyuk S, Egolina N, Efremova L, Veiko N. Oxidative stress as a significant factor for development of an adaptive response in irradiated and nonirradiated human lymphocytes after inducing the bystander effect by low-dose X-radiation. Mutat Res. 2009;669:155-61 pubmed publisher
    ..We thus believe that ecDNA of irradiated apoptotic lymphocytes is a significant factor of stress-signalling. ..
  32. Kleinnijenhuis J, Joosten L, van de Veerdonk F, Savage N, van Crevel R, Kullberg B, et al. Transcriptional and inflammasome-mediated pathways for the induction of IL-1beta production by Mycobacterium tuberculosis. Eur J Immunol. 2009;39:1914-22 pubmed publisher
    ..In conclusion, we have dissected the molecular mechanisms responsible for IL-1beta production by M. tuberculosis, and that may contribute to a deeper knowledge of the mechanisms of cell activation by M. tuberculosis. ..
  33. Cagigi A, Du L, Dang L, Grutzmeier S, Atlas A, Chiodi F, et al. CD27(-) B-cells produce class switched and somatically hyper-mutated antibodies during chronic HIV-1 infection. PLoS ONE. 2009;4:e5427 pubmed publisher
    ..Our data add important information for the understanding of the mechanisms underlying the loss of specific antibody production observed during HIV-1 infection. ..
  34. Bereczky Veress B, Abdelmagid N, Piehl F, Bergstrom T, Olsson T, Sköldenberg B, et al. Influence of perineurial cells and Toll-like receptors 2 and 9 on Herpes simplex type 1 entry to the central nervous system in rat encephalitis. PLoS ONE. 2010;5:e12350 pubmed publisher
  35. Tanaka J, Sugimoto K, Shiraki K, Tameda M, Kusagawa S, Nojiri K, et al. Functional cell surface expression of toll-like receptor 9 promotes cell proliferation and survival in human hepatocellular carcinomas. Int J Oncol. 2010;37:805-14 pubmed
    ..In conclusion, our results indicate that functional cell surface expression of TLR9 in human HCC may play an important role in tumorigenesis and cancer progression. ..
  36. Coch C, Busch N, Wimmenauer V, Hartmann E, Janke M, Abdel Mottaleb M, et al. Higher activation of TLR9 in plasmacytoid dendritic cells by microbial DNA compared with self-DNA based on CpG-specific recognition of phosphodiester DNA. J Leukoc Biol. 2009;86:663-70 pubmed publisher
  37. Doi Y, Mizuno T, Maki Y, Jin S, Mizoguchi H, Ikeyama M, et al. Microglia activated with the toll-like receptor 9 ligand CpG attenuate oligomeric amyloid {beta} neurotoxicity in in vitro and in vivo models of Alzheimer's disease. Am J Pathol. 2009;175:2121-32 pubmed publisher
    ..We propose that CpG may be an effective therapeutic strategy for limiting oAbeta1-42 neurotoxicity in AD. ..
  38. Klekotka P, Yang L, Yokoyama W. Contrasting roles of the IL-1 and IL-18 receptors in MyD88-dependent contact hypersensitivity. J Invest Dermatol. 2010;130:184-91 pubmed publisher
    ..Taken together, these data indicate that the IL-1R and IL-18R/MyD88 pathways are required in distinctly different cells during the sensitization phase of CHS. ..
  39. Wakchoure S, Swain T, Hentunen T, Bauskin A, Brown D, Breit S, et al. Expression of macrophage inhibitory cytokine-1 in prostate cancer bone metastases induces osteoclast activation and weight loss. Prostate. 2009;69:652-61 pubmed publisher
    ..MIC-1 stimulates both osteoblast and osteoclast differentiation in vitro, independently of TLR9. MIC-1 over-expressing prostate cancer cells that grow in bone induce osteoclast formation and cachexia. ..
  40. Dil N, Marshall A. Role of phosphoinositide 3-kinase p110 delta in TLR4- and TLR9-mediated B cell cytokine production and differentiation. Mol Immunol. 2009;46:1970-8 pubmed publisher
    ..Together, these results indicate that PI3K delta functions in influencing the type of B cell cytokine production and differentiation response induced by TLR-ligands. ..
  41. Chiron D, Jego G, Pellat Deuceunynck C. Toll-like receptors: expression and involvement in multiple myeloma. Leuk Res. 2010;34:1545-50 pubmed publisher
    ..This review is focused on the heterogeneous expression and function of TLRs in MM and on the potential implication of TLR ligands of infectious or endogenous origin in MM emergence, resistance, or progression. ..
  42. O Neill S, Veselits M, Zhang M, Labno C, Cao Y, Finnegan A, et al. Endocytic sequestration of the B cell antigen receptor and toll-like receptor 9 in anergic cells. Proc Natl Acad Sci U S A. 2009;106:6262-7 pubmed publisher
    ..These results indicate that B cell anergy is reinforced by the exclusion of both TLRs and their BCR captured ligands from subcellular environments necessary for TLR activation. ..
  43. Kim Y, Girardi M, Duvic M, Kuzel T, Link B, Pinter Brown L, et al. Phase I trial of a Toll-like receptor 9 agonist, PF-3512676 (CPG 7909), in patients with treatment-refractory, cutaneous T-cell lymphoma. J Am Acad Dermatol. 2010;63:975-83 pubmed publisher
    ..This trial was not designed to rigorously assess efficacy. Single-agent PF-3512676 was well tolerated and demonstrated antitumor activity in patients with refractory CTCL. ..
  44. Mahanonda R, Sa Ard Iam N, Eksomtramate M, Rerkyen P, Phairat B, Schaecher K, et al. Cigarette smoke extract modulates human beta-defensin-2 and interleukin-8 expression in human gingival epithelial cells. J Periodontal Res. 2009;44:557-64 pubmed publisher
    ..Our results represent the first demonstration that CSE can modulate HGEC function by suppressing hBD-2 and enhancing IL-8 production, and this may be, in part, a possible mechanism which promotes periodontal disease. ..
  45. Putta M, Yu D, Bhagat L, Wang D, Zhu F, Kandimalla E. Impact of nature and length of linker incorporated in agonists on toll-like receptor 9-mediated immune responses. J Med Chem. 2010;53:3730-8 pubmed publisher
    ..Rigid C3 linkers with different stereochemistry have little effect on immune stimulation, while linkers longer than C5 reduced TLR9-mediated immune stimulation. ..
  46. Berger R, Fiegl H, Goebel G, Obexer P, Ausserlechner M, Doppler W, et al. Toll-like receptor 9 expression in breast and ovarian cancer is associated with poorly differentiated tumors. Cancer Sci. 2010;101:1059-66 pubmed publisher
  47. van Endert P. Toll-like receptor 9: AEP takes control. Immunity. 2009;31:696-8 pubmed publisher
    ..In this issue of Immunity, Sepulveda et al. (2009) demonstrate that in dendritic cells, asparaginyl endopeptidase is a key protease that controls TLR9 maturation. ..
  48. Yew K, Carsten B, Harrison C. Scavenger receptor A1 is required for sensing HCMV by endosomal TLR-3/-9 in monocytic THP-1 cells. Mol Immunol. 2010;47:883-93 pubmed publisher
    ..These findings reveal a novel mechanistic insight into an interrelationship between SR-A1 and TLR-3/-9 signaling in HCMV-exposed monocytes. ..
  49. Nayak S, Herzog R. Progress and prospects: immune responses to viral vectors. Gene Ther. 2010;17:295-304 pubmed publisher
    ..This review provides a summary of our current knowledge of the interactions between the immune system adeno-associated virus, adenoviral and lentiviral vectors, and their transgene products. ..
  50. Padilla A, Simpson L, Tarleton R. Insufficient TLR activation contributes to the slow development of CD8+ T cell responses in Trypanosoma cruzi infection. J Immunol. 2009;183:1245-52 pubmed publisher
    ..cruzi by administration of ligands for TLR2 and TLR9 at the time of infection. These studies highlight a previously unappreciated mechanism of immune evasion, the surreptitious establishment of infection, by the protozoan T. cruzi. ..
  51. Hreggvidsdottir H, Ostberg T, Wähämaa H, Schierbeck H, Aveberger A, Klevenvall L, et al. The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammation. J Leukoc Biol. 2009;86:655-62 pubmed publisher
    ..HMGB1 thus acts broadly with many but not all immunostimulatory molecules to amplify their activity in a synergistic manner. ..
  52. Jing Y, Shaheen E, Drake R, Chen N, Gravenstein S, Deng Y. Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood. Hum Immunol. 2009;70:777-84 pubmed publisher
  53. Ito T, Schaller M, Raymond T, Joshi A, Coelho A, Frantz F, et al. Toll-like receptor 9 activation is a key mechanism for the maintenance of chronic lung inflammation. Am J Respir Crit Care Med. 2009;180:1227-38 pubmed publisher
    ..These studies suggest that TLR9 plays an important mechanistic role in the maintenance of the pulmonary granulomatous response. ..