更新于：2024-04-01
TLR8
Toll样受体8
更新于：2024-04-01
基本信息
别名 类Toll受体8、CD288、hTLR8 + [3] |
简介 Endosomal receptor that plays a key role in innate and adaptive immunity (PubMed:25297876, PubMed:32433612). Controls host immune response against pathogens through recognition of RNA degradation products specific to microorganisms that are initially processed by RNASET2 (PubMed:31778653). Recognizes GU-rich single-stranded RNA (GU-rich RNA) derived from SARS-CoV-2, SARS-CoV-1 and HIV-1 viruses (PubMed:33718825). Upon binding to agonists, undergoes dimerization that brings TIR domains from the two molecules into direct contact, leading to the recruitment of TIR-containing downstream adapter MYD88 through homotypic interaction (PubMed:23520111, PubMed:25599397, PubMed:26929371, PubMed:33718825). In turn, the Myddosome signaling complex is formed involving IRAK4, IRAK1, TRAF6, TRAF3 leading to activation of downstream transcription factors NF-kappa-B and IRF7 to induce pro-inflammatory cytokines and interferons, respectively (PubMed:16737960, PubMed:17932028, PubMed:29155428). |
关联
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of Afimetoran in Participants with Active Systemic Lupus Erythematosus - NIL
A Phase 2 Study of EIK1001 in Combination With Pembrolizumab and Chemotherapy in Patients With Stage 4 Non-Small Cell Lung Cancer
Clinical study on the safety, tolerability, and preliminary efficacy of BM201 injection combined with radiation therapy and PD-1 monoclonal antibody in patients with advanced solid tumors
100 项与 TLR8 相关的临床结果
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100 项与 TLR8 相关的转化医学
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2024-12-31Human vaccines & immunotherapeutics
From defense to offense: Modulating toll-like receptors to combat arbovirus infections.
Review
作者: Rafidah Lani ; Ilya Maisarah Thariq ; Nuramira Syazreen Suhaimi ; Pouya Hassandarvish ; Sazaly Abu Bakar
Arboviruses are a significant threat to global public health, with outbreaks occurring worldwide. Toll-like receptors (TLRs) play a crucial role in the innate immune response against these viruses by recognizing pathogen-associated molecular patterns and initiating an inflammatory response. Significantly, TLRs commonly implicated in the immune response against viral infections include TLR2, TLR4, TLR6, TLR3, TLR7, and TLR8; limiting or allowing them to replicate and spread within the host. Modulating TLRs has emerged as a promising approach to combat arbovirus infections. This review summarizes recent advances in TLR modulation as a therapeutic target in arbovirus infections. Studies have shown that the activation of TLRs can enhance the immune response against arbovirus infections, leading to increased viral clearance and protection against disease. Conversely, inhibition of TLRs can reduce the excessive inflammation and tissue damage associated with arbovirus infection. Modulating TLRs represents a potential therapeutic strategy to combat arbovirus infections.
2024-02-17Nutrients
Vitamin D Status, VDR, and TLR Polymorphisms and Pulmonary Tuberculosis Epidemiology in Kazakhstan.
Article
作者: Dauren Yerezhepov ; Aidana Gabdulkayum ; Ainur Akhmetova ; Ulan A Kozhamkulov ; Saule E Rakhimova ; Ulykbek Y Kairov ; Gulnur Zhunussova ; Ruslan N Kalendar ; Ainur Akilzhanova
BACKGROUND:
Tuberculosis (TB) and vitamin D deficiency remain major public health problems in Kazakhstan. Due to the high incidence of pulmonary tuberculosis in the country and based on the importance of vitamin D in the modulation of the immune response and the association of its deficiency with many health conditions, the aim of our research was to study the vitamin D status, VDR and TLR gene polymorphisms, and pulmonary tuberculosis epidemiology in Kazakhstan.
METHODS:
A case-control study included 411 individuals diagnosed with pulmonary TB and 686 controls with no family history of pulmonary tuberculosis. Concentrations of serum vitamin D (25-(OH)D) levels were measured by electrochemiluminescence immunoassay. The gene polymorphisms were determined by real-time polymerase chain reaction (PCR) allelic discrimination assay using TaqMan probes. The association between the risk of pulmonary TB and polymorphisms was evaluated using multimodal logistic regression and assessed with the ORs, corresponding to 95% Cis, and the significance level was determined as p < 0.05.
RESULTS:
1097 individuals were recruited from 3 different regions of Kazakhstan. Biochemical data showed vitamin D deficiency (25-(OH)D < 20 ng/mL) was present in both groups, with the case group accounting for almost 95% and 43.7% in controls. Epidemiological data revealed that socioeconomic factors such as BMI < 25 kg/m2 (p < 0.001), employment (p < 0.001), diabetes (p < 0.001), and vitamin D deficiency (p < 0.001) were statistically different between case and control groups. Logistic regression analysis, adjusted by sex, age, BMI, residence, employment, smoking, alcohol consumption, and diabetes, showed that T/T polymorphism of the VDR gene (rs1544410, OR = 1.97, 95% CI: 1.04-3.72, p = 0.03) and A/A polymorphism of the TLR8 gene (rs3764880, OR = 2.44, 95% CI: 1.20-4.98, p = 0.01) were associated with a high risk of developing pulmonary tuberculosis.
CONCLUSIONS:
Vitamin D deficiency remains prevalent in our study cohort and is associated with TB progression. Socioeconomic determinants such as unemployment, BMI under 25 kg/m2, and diabetes are the main risk factors for the development of pulmonary TB in our study. A/A polymorphism of TLR8 (rs3764880) and T/T polymorphism (BsmI, rs1544410) of VDR genes may act as biomarkers for pulmonary tuberculosis in the Kazakh population.
2024-02-15JCI insight
Combining antibiotic with anti-TLR2/TLR13 therapy prevents brain pathology in pneumococcal meningitis.
Article
作者: Susanne Dyckhoff-Shen ; Ilias Masouris ; Heba Islam ; Sven Hammerschmidt ; Barbara Angele ; Veena Marathe ; Jan Buer ; Stefanie Völk ; Hans-Walter Pfister ; Matthias Klein ; Uwe Koedel ; Carsten J Kirschning
Despite effective antibiotic therapy, brain destructive inflammation often cannot be avoided in pneumococcal meningitis. The causative signals are mediated predominantly through TLR recruited myeloid differentiation primary response adaptor (MyD) 88 as indicated by a dramatic pneumococcal meningitis phenotype of Myd88-/- mice. Because lipoproteins and ssRNA are crucial for recognition of Gram-positive bacteria such as Streptococcus pneumoniae by the host immune system, we comparatively analyzed the disease courses of Myd88-/- and Tlr2/13-/- mice. Their phenotype resemblance indicated TLR2 and -13 as master sensors of Streptococcus pneumoniae in the cerebrospinal fluid. The neutralizing anti-TLR2 antibody (T2.5) and chloroquine (CQ) - the latter applied here as an inhibitor for murine TLR13 and its human orthologue TLR8 - abrogated activation of murine and human primary immune cells exposed to antibiotic-treated Streptococcus pneumoniae. The inhibitory effect of the T2.5/CQ cocktail was stronger than that of dexamethasone, the current standard adjunctive drug for pneumococcal meningitis. Accordingly, TLR2/13 blockade concomitant with ceftriaxone application significantly improved the clinical course of pneumococcal meningitis compared to treatment with ceftriaxone alone or in combination with dexamethasone. Our study implicates the importance of murine TLR13 and human TLR8, besides TLR2, in pneumococcal meningitis pathology, and suggests their blockade as a promising antibiotic therapy adjunct.
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