{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nToll‐like receptor 9 (TLR9) is a crucial component of the innate immune system that recognizes unmethylated CpG dinucleotides abundant in microbial DNA. In resting cells, TLR9 is predominantly sequestered in the endoplasmic reticulum; upon encounter with CpG‐containing ligands, it translocates to specialized endosomal compartments where it directly binds DNA and recruits the MyD88 adaptor protein, thereby initiating NF‐κB–dependent inflammatory signaling. Moreover, studies using reconstituted cell systems have demonstrated that TLR9 expression can be induced by receptor triggering and that its ligand recognition is modulated by extracellular factors—such as changes in endosomal pH and the action of nucleic acid–binding inhibitors—underscoring a finely tuned mechanism of signal initiation and amplification."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in pathogen sensing, TLR9 orchestrates key innate responses that bridge to adaptive immunity. In plasmacytoid dendritic cells and other antigen‐presenting cells, recognition of both microbial and self–DNA—frequently delivered in the context of immune complexes—results in robust production of type I interferons and proinflammatory cytokines. Genetic analyses have revealed polymorphisms within the TLR9 gene that influence susceptibility to disorders such as systemic lupus erythematosus, malaria, and allergic conditions, while noncanonical processes such as LC3‐associated phagocytosis regulate the trafficking of TLR9 into specialized signaling compartments. Collectively, these observations emphasize that precise modulation of TLR9 responses is critical for balancing effective antimicrobial defense against the risk of chronic inflammation and autoimmunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTLR9 expression is not confined solely to professional immune cells but is also observed in diverse nonimmune tissues, where its dysregulation contributes to a spectrum of pathological states. In tumor cells, elevated TLR9 has been linked to enhanced invasiveness and modulation of the tumor microenvironment, while in organs such as the liver, lung, and kidney, aberrant activation of TLR9 is associated with fibrotic remodeling and chronic inflammation. In addition, recent evidence implicates TLR9 in the regulation of platelet reactivity, neuronal pain signaling, and even autophagic flux via recognition of mitochondrial DNA—pointing to a broad influence on both homeostatic and disease‐related processes. These multifaceted roles of TLR9 highlight its potential as a therapeutic target in conditions ranging from chronic viral infections and autoimmune diseases to cancer and degenerative disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "31", "end_ref": "40"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tsung-Hsien Chuang, Jongdae Lee, Lois Kline, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Human lung cancer cells express functionally active Toll-like receptor 9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Respir Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1465-9921-6-1"}], "href": "https://doi.org/10.1186/1465-9921-6-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15631627"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15631627"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "John T Schroeder, Anja P Bieneman, Huiqing Xiao, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Activation of toll-like receptor 9 by DNA from different bacterial species."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Infect Immun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/IAI.74.2.940-946.2006"}], "href": "https://doi.org/10.1128/IAI.74.2.940-946.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16428738"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16428738"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Trine H Mogensen, Søren R Paludan, Mogens Kilian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Live Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis activate the inflammatory response through Toll-like receptors 2, 4, and 9 in species-specific patterns."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Leukoc Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1189/jlb.1105626"}], "href": "https://doi.org/10.1189/jlb.1105626"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16731773"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16731773"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ross Lazarus, Walter T Klimecki, Benjamin A Raby, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Single-nucleotide polymorphisms in the Toll-like receptor 9 gene (TLR9): frequencies, pairwise linkage disequilibrium, and haplotypes in three U.S. ethnic groups and exploratory case-control disease association studies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0888-7543(02)00022-8"}], "href": "https://doi.org/10.1016/s0888-7543(02"}, {"type": "t", "text": "00022-8) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12573264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12573264"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Franck J Barrat, Thea Meeker, Josh Gregorio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20050914"}], "href": "https://doi.org/10.1084/jem.20050914"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16230478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16230478"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Frank P Mockenhaupt, Jakob P Cramer, Lutz Hamann, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20060401"}], "href": "https://doi.org/10.1084/jem.20060401"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16864658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16864658"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Andre Bafica, Helton Costa Santiago, Romina Goldszmid, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.177.6.3515"}], "href": "https://doi.org/10.4049/jimmunol.177.6.3515"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16951309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16951309"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Eva D Papadimitraki, Christianna Choulaki, Eleni Koutala, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expansion of toll-like receptor 9-expressing B cells in active systemic lupus erythematosus: implications for the induction and maintenance of the autoimmune process."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/art.22197"}], "href": "https://doi.org/10.1002/art.22197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17075805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17075805"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Kayoko Tao, Mutsuko Fujii, Shin-ichi Tsukumo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variations of Toll-like receptor 9 predispose to systemic lupus erythematosus in Japanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Rheum Dis (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/ard.2006.065961"}], "href": "https://doi.org/10.1136/ard.2006.065961"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17344245"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17344245"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "N Novak, C-F Yu, C Bussmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Putative association of a TLR9 promoter polymorphism with atopic eczema."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Allergy (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1398-9995.2007.01358.x"}], "href": "https://doi.org/10.1111/j.1398-9995.2007.01358.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17573724"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17573724"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Yutaro Kumagai, Osamu Takeuchi, Shizuo Akira "}, {"type": "b", "children": [{"type": "t", "text": "TLR9 as a key receptor for the recognition of DNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Drug Deliv Rev (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.addr.2007.12.004"}], "href": "https://doi.org/10.1016/j.addr.2007.12.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18262306"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18262306"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "A Carvalho, A C Pasqualotto, L Pitzurra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in toll-like receptor genes and susceptibility to pulmonary aspergillosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Infect Dis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/526500"}], "href": "https://doi.org/10.1086/526500"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18275280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18275280"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Zaida G Ramirez-Ortiz, Charles A Specht, Jennifer P Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Toll-like receptor 9-dependent immune activation by unmethylated CpG motifs in Aspergillus fumigatus DNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Infect Immun (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/IAI.00047-08"}], "href": "https://doi.org/10.1128/IAI.00047-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18332208"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18332208"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Hitoshi Suzuki, Yusuke Suzuki, Ichiei Narita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Toll-like receptor 9 affects severity of IgA nephropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2007121311"}], "href": "https://doi.org/10.1681/ASN.2007121311"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18776126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18776126"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Judith N Mandl, Ashley P Barry, Thomas H Vanderford, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.1871"}], "href": "https://doi.org/10.1038/nm.1871"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18806803"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18806803"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Henrieta Scholtzova, Richard J Kascsak, Kristyn A Bates, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Induction of toll-like receptor 9 signaling as a method for ameliorating Alzheimer's disease-related pathology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.5715-08.2009"}], "href": "https://doi.org/10.1523/JNEUROSCI.5715-08.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19211891"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19211891"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Bernardo S Franklin, Peggy Parroche, Marco Antonio Ataíde, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Malaria primes the innate immune response due to interferon-gamma induced enhancement of toll-like receptor expression and function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0809742106"}], "href": "https://doi.org/10.1073/pnas.0809742106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19297619"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19297619"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Wei Cao, Laura Bover, Minkwon Cho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20090547"}], "href": "https://doi.org/10.1084/jem.20090547"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19564354"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19564354"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Alexandra-Chloé Villani, Mathieu Lemire, Marroon Thabane, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic risk factors for post-infectious irritable bowel syndrome following a waterborne outbreak of gastroenteritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2009.12.049"}], "href": "https://doi.org/10.1053/j.gastro.2009.12.049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20044998"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20044998"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Alexander Panda, Feng Qian, Subhasis Mohanty, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0901022"}], "href": "https://doi.org/10.4049/jimmunol.0901022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20100933"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20100933"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Cristiana Guiducci, Mei Gong, Zhaohui Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09102"}], "href": "https://doi.org/10.1038/nature09102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20559388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20559388"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Alenka Kuznik, Mojca Bencina, Urban Svajger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1000702"}], "href": "https://doi.org/10.4049/jimmunol.1000702"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21398612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21398612"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Jill Henault, Jennifer Martinez, Jeffrey M Riggs, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Noncanonical autophagy is required for type I interferon secretion in response to DNA-immune complexes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2012.09.014"}], "href": "https://doi.org/10.1016/j.immuni.2012.09.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23219390"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23219390"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Glenda Trujillo, Alessia Meneghin, Kevin R Flaherty, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-10-665"}], "href": "https://doi.org/10.1186/1471-2407-10-665"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21129170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21129170"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Jia Qi, Krisztina Buzas, Huiting Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Painful pathways induced by TLR stimulation of dorsal root ganglion neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1001241"}], "href": "https://doi.org/10.4049/jimmunol.1001241"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21515789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21515789"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Shin Morizane, Kenshi Yamasaki, Beda Mühleisen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2011.259"}], "href": "https://doi.org/10.1038/jid.2011.259"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21850017"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21850017"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Isabelle E Vincent, Claudia Zannetti, Julie Lucifora, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0026315"}], "href": "https://doi.org/10.1371/journal.pone.0026315"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22046272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22046272"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Soumya Panigrahi, Yi Ma, Li Hong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Engagement of platelet toll-like receptor 9 by novel endogenous ligands promotes platelet hyperreactivity and thrombosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.112.274241"}], "href": "https://doi.org/10.1161/CIRCRESAHA.112.274241"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23071157"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23071157"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Uzma A Hasan, Claudia Zannetti, Peggy Parroche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human papillomavirus type 16 E7 oncoprotein induces a transcriptional repressor complex on the Toll-like receptor 9 promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20122394"}], "href": "https://doi.org/10.1084/jem.20122394"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23752229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23752229"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Yoon Seok Roh, Ekihiro Seki "}, {"type": "b", "children": [{"type": "t", "text": "Toll-like receptors in alcoholic liver disease, non-alcoholic steatohepatitis and carcinogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gastroenterol Hepatol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jgh.12019"}], "href": "https://doi.org/10.1111/jgh.12019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23855294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23855294"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Dewan M S Hossain, Sumanta K Pal, Dayson Moreira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TLR9-Targeted STAT3 Silencing Abrogates Immunosuppressive Activity of Myeloid-Derived Suppressor Cells from Prostate Cancer Patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-14-3145"}], "href": "https://doi.org/10.1158/1078-0432.CCR-14-3145"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25967142"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25967142"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Maria Giovanna De Leo, Leopoldo Staiano, Mariella Vicinanza, et al. 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