{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTLR8 functions as an intracellular sensor for single‐stranded RNA—in particular, GU‐rich sequences derived from viral genomes (e.g. HIV‐1) and bacterial RNA—that are generated or “edited” by host ribonucleases in acidified endosomal compartments. Structural studies have revealed that ligand binding induces a profound reorganization of the receptor dimer, a process that is dependent on a conserved ectodomain motif and favorable low‐pH conditions. In addition, endolysosomal RNases such as RNase T2 and RNase 2 process complex RNA molecules, generating the uridine‐containing degradation products that serve as optimal ligands for TLR8."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nUpon ligand engagement, TLR8 transduces signals via a MyD88‐dependent pathway that involves the recruitment of signaling intermediates—such as IRAK, MEKK3, and IκB kinases—and culminates in the activation of NF‐κB and interferon regulatory factors. Such activation leads to a robust production of proinflammatory cytokines (for example, TNF‐α, IL‐1β, IL‐12 and type I interferons) and can be modulated by synergistic interactions with other TLRs (including TLR3 and TLR4) as well as additional accessory receptors. Differential signaling cascades downstream of TLR8 have been documented in various human antigen‐presenting cells (monocytes, dendritic cells) and are critical in tailoring both antiviral responses and subsequent T‐cell polarization outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in antiviral defense, aberrant or dysregulated TLR8 signaling contributes to a wide range of pathophysiological conditions. For instance, its activity can overturn regulatory T‐cell function to enhance antitumor immunity, while expression of TLR8 by tumor cells may activate NF‐κB and promote cell survival and chemoresistance. In monocytes and dendritic cells, TLR8 activation not only drives inflammatory cytokine release but also interfaces with receptors such as DC‐SIGN to modulate viral replication (as in HIV‐1 infection) and acute inflammatory responses in conditions like myocarditis and psoriasis. Moreover, genetic polymorphisms in the TLR8 gene have been linked with susceptibility to infectious diseases (including tuberculosis) and autoimmune disorders (such as systemic lupus erythematosus, rheumatoid arthritis and antiphospholipid syndrome), and emerging evidence implicates TLR8 in shaping vaccine responses as well as in neurodegenerative processes by sensing endogenous retroviral RNAs."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Florian Heil, Hiroaki Hemmi, Hubertus Hochrein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1093620"}], "href": "https://doi.org/10.1126/science.1093620"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14976262"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14976262"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hiromi Tanji, Umeharu Ohto, Takuma Shibata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1229159"}], "href": "https://doi.org/10.1126/science.1229159"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23520111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23520111"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anne Krüger, Marina Oldenburg, Chiranjeevi Chebrolu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human TLR8 senses UR/URR motifs in bacterial and mitochondrial RNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201540861"}], "href": "https://doi.org/10.15252/embr.201540861"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26545385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26545385"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Rebecca J Gibbard, Peter J Morley, Nicholas J Gay "}, {"type": "b", "children": [{"type": "t", "text": "Conserved features in the extracellular domain of human toll-like receptor 8 are essential for pH-dependent signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M605003200"}], "href": "https://doi.org/10.1074/jbc.M605003200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16857668"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16857668"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tatjana Eigenbrod, Karin Pelka, Eicke Latz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TLR8 Senses Bacterial RNA in Human Monocytes and Plays a Nonredundant Role for Recognition of Streptococcus pyogenes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1403173"}], "href": "https://doi.org/10.4049/jimmunol.1403173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26101323"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26101323"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sonja I Gringhuis, Michiel van der Vlist, Linda M van den Berg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HIV-1 exploits innate signaling by TLR8 and DC-SIGN for productive infection of dendritic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.1858"}], "href": "https://doi.org/10.1038/ni.1858"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20364151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20364151"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kathy Triantafilou, George Orthopoulos, Emmanouil Vakakis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human cardiac inflammatory responses triggered by Coxsackie B viruses are mainly Toll-like receptor (TLR) 8-dependent."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Microbiol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1462-5822.2005.00537.x"}], "href": "https://doi.org/10.1111/j.1462-5822.2005.00537.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16008579"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16008579"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Haitao Guo, Jianmei Gao, Debra J Taxman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HIV-1 infection induces interleukin-1β production via TLR8 protein-dependent and NLRP3 inflammasome mechanisms in human monocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.566620"}], "href": "https://doi.org/10.1074/jbc.M114.566620"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24939850"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24939850"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sanna M Mäkelä, Mari Strengell, Taija E Pietilä, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multiple signaling pathways contribute to synergistic TLR ligand-dependent cytokine gene expression in human monocyte-derived macrophages and dendritic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Leukoc Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1189/jlb.0808503"}], "href": "https://doi.org/10.1189/jlb.0808503"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19164128"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19164128"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Marine de Marcken, Khushwant Dhaliwal, Ann Caroline Danielsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.aaw1347"}], "href": "https://doi.org/10.1126/scisignal.aaw1347"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31662487"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31662487"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jinzhong Qin, Jianhong Yao, Grace Cui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TLR8-mediated NF-kappaB and JNK activation are TAK1-independent and MEKK3-dependent."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M512908200"}], "href": "https://doi.org/10.1074/jbc.M512908200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16737960"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16737960"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Andrea Ablasser, Hendrik Poeck, David Anz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selection of molecular structure and delivery of RNA oligonucleotides to activate TLR7 versus TLR8 and to induce high amounts of IL-12p70 in primary human monocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0803001"}], "href": "https://doi.org/10.4049/jimmunol.0803001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19454678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19454678"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Vincent Lombardi, Laurence Van Overtvelt, Stéphane Horiot, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human dendritic cells stimulated via TLR7 and/or TLR8 induce the sequential production of Il-10, IFN-gamma, and IL-17A by naive CD4+ T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0801969"}], "href": "https://doi.org/10.4049/jimmunol.0801969"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19265114"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19265114"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Laura Q M Chow, Chihiro Morishima, Keith D Eaton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phase Ib Trial of the Toll-like Receptor 8 Agonist, Motolimod (VTX-2337), Combined with Cetuximab in Patients with Recurrent or Metastatic SCCHN."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-16-1934"}], "href": "https://doi.org/10.1158/1078-0432.CCR-16-1934"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27810904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27810904"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Jérôme Cros, Nicolas Cagnard, Kevin Woollard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2010.08.012"}], "href": "https://doi.org/10.1016/j.immuni.2010.08.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20832340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20832340"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Guangyong Peng, Zhong Guo, Yukiko Kiniwa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1113401"}], "href": "https://doi.org/10.1126/science.1113401"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16123302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16123302"}]}, {"type": "r", "ref": 17, "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": 18, "children": [{"type": "t", "text": "Barry Flutter, Frank O Nestle "}, {"type": "b", "children": [{"type": "t", "text": "TLRs to cytokines: mechanistic insights from the imiquimod mouse model of psoriasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.201343801"}], "href": "https://doi.org/10.1002/eji.201343801"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24254490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24254490"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Sonia Davila, Martin L Hibberd, Ranjeeta Hari Dass, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic association and expression studies indicate a role of toll-like receptor 8 in pulmonary tuberculosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1000218"}], "href": "https://doi.org/10.1371/journal.pgen.1000218"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18927625"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18927625"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Julien Cherfils-Vicini, Sophia Platonova, Mélanie Gillard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI36551"}], "href": "https://doi.org/10.1172/JCI36551"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20237413"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20237413"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "G Comito, A Iscaro, M Bacci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lactate modulates CD4"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " T-cell polarization and induces an immunosuppressive environment, which sustains prostate carcinoma progression via TLR8/miR21 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-019-0688-7"}], "href": "https://doi.org/10.1038/s41388-019-0688-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30664688"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30664688"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Pierre-Yves Bochud, Martin Hersberger, Patrick Taffé, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in Toll-like receptor 9 influence the clinical course of HIV-1 infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "AIDS (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/QAD.0b013e328012b8ac"}], "href": "https://doi.org/10.1097/QAD.0b013e328012b8ac"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17301562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17301562"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Chin-Man Wang, Su-Wei Chang, Yeong-Jian Jan Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variations in Toll-like receptors (TLRs 3/7/8) are associated with systemic lupus erythematosus in a Taiwanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep03792"}], "href": "https://doi.org/10.1038/srep03792"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24445780"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24445780"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Simon D van Haren, David J Dowling, Willemina Foppen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Age-Specific Adjuvant Synergy: Dual TLR7/8 and Mincle Activation of Human Newborn Dendritic Cells Enables Th1 Polarization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1600282"}], "href": "https://doi.org/10.4049/jimmunol.1600282"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27793997"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27793997"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Jianyong Wang, Yu Shao, Teri A Bennett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The functional effects of physical interactions among Toll-like receptors 7, 8, and 9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M605311200"}], "href": "https://doi.org/10.1074/jbc.M605311200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17040905"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17040905"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Matteo Ugolini, Jenny Gerhard, Sanne Burkert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recognition of microbial viability via TLR8 drives T"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "FH"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": " cell differentiation and vaccine responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41590-018-0068-4"}], "href": "https://doi.org/10.1038/s41590-018-0068-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29556002"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29556002"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Nadine Prinz, Natascha Clemens, Dennis Strand, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Antiphospholipid antibodies induce translocation of TLR7 and TLR8 to the endosome in human monocytes and plasmacytoid dendritic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-01-330639"}], "href": "https://doi.org/10.1182/blood-2011-01-330639"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21734241"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21734241"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Friederike Meyer-Wentrup, Alessandra Cambi, Ben Joosten, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DCIR is endocytosed into human dendritic cells and inhibits TLR8-mediated cytokine production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Leukoc Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1189/jlb.0608352"}], "href": "https://doi.org/10.1189/jlb.0608352"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19028959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19028959"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Sandra M Sacre, Alexandra Lo, Bernard Gregory, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibitors of TLR8 reduce TNF production from human rheumatoid synovial membrane cultures."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.181.11.8002"}], "href": "https://doi.org/10.4049/jimmunol.181.11.8002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19017992"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19017992"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Pei-Lin Cheng, Hock-Liew Eng, Ming-Huei Chou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic polymorphisms of viral infection-associated Toll-like receptors in Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transl Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.trsl.2007.03.010"}], "href": "https://doi.org/10.1016/j.trsl.2007.03.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17964520"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17964520"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Jin Liu, Congfeng Xu, Li-Chung Hsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A five-amino-acid motif in the undefined region of the TLR8 ectodomain is required for species-specific ligand recognition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2009.11.003"}], "href": "https://doi.org/10.1016/j.molimm.2009.11.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20004021"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20004021"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Klára Sochorová, Rudolf Horváth, Daniela Rozková, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impaired Toll-like receptor 8-mediated IL-6 and TNF-alpha production in antigen-presenting cells from patients with X-linked agammaglobulinemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2006-07-037960"}], "href": "https://doi.org/10.1182/blood-2006-07-037960"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17090647"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17090647"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Paul Dembny, Andrew G Newman, Manvendra Singh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JCI Insight (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/jci.insight.131093"}], "href": "https://doi.org/10.1172/jci.insight.131093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32271161"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32271161"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Gavin E Morris, Lisa C Parker, Jon R Ward, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cooperative molecular and cellular networks regulate Toll-like receptor-dependent inflammatory responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.06-5910fje"}], "href": "https://doi.org/10.1096/fj.06-5910fje"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16935934"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16935934"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Christian Lood, Sabine Arve, Jeffrey Ledbetter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TLR7/8 activation in neutrophils impairs immune complex phagocytosis through shedding of FcgRIIA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20161512"}], "href": "https://doi.org/10.1084/jem.20161512"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28606989"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28606989"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Y H Lee, S J Choi, J D Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between toll-like receptor polymorphisms and systemic lupus erythematosus: a meta-analysis update."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lupus (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0961203315622823"}], "href": "https://doi.org/10.1177/0961203315622823"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26762473"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26762473"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Andrew T Bender, Evgeni Tzvetkov, Albertina Pereira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TLR7 and TLR8 Differentially Activate the IRF and NF-κB Pathways in Specific Cell Types to Promote Inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunohorizons (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/immunohorizons.2000002"}], "href": "https://doi.org/10.4049/immunohorizons.2000002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32086319"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32086319"}]}]}]}