Top Tweets for #TLR8
Patel, Cooper, Zimmerman et al. describe an elderly woman w/ severe chronic #neutropenia caused by mosaic #TLR8 GOF, broadening a primarily pediatric, male disease spectrum & highlighting somatic mosaicism as an important diagnostic consideration https://t.co/1WzxI2SUNj
#IEIs
#TLR8 antagonists ―small-molecule inhibitors designed to block this key sensor of single-stranded RNA― are being explored for their therapeutic potential in a variety of medical conditions. One of the most promising areas of research is in #autoimmune diseases. Leading research-grade antagonists include CU-CPT9a (IC50 ~0.5 nM) and CU-CPT8m, which stabilize the receptor in an inactive state. While candidates like Enpatoran (M5049) are in clinical trials for autoimmune conditions like systemic #lupus erythematosus (SLE), most highly selective TLR8 antagonists remain in preclinical or tool-compound phases.
Key TLR8 antagonist compounds:
◦ CU-CPT9a, 9b, 9c: Extremely potent quinoline-based inhibitors with subnanomolar IC50 values.
◦ CU-CPT8m: A selective TLR8 inhibitor that functions by stabilizing the resting state of the receptor.
◦ Enpatoran (M5049): A dual TLR7/8 antagonist currently investigated for autoimmune disease management.
These antagonists often target an unconventional pocket on the TLR8 protein-protein interface, distinct from the agonist binding site. By binding to this site, they prevent the conformational changes required for receptor activation, thereby reducing pro-inflammatory cytokine production. Structural differences between TLR7 and TLR8 allow for the design of inhibitors that specifically block TLR8 without affecting TLR7.
Current TLR8 antagonists research focuses on mitigating hyperinflammation in autoimmune diseases, such as SLE and #rheumatoid #arthritis. However, other chronic inflammatory conditions, including COPD and asthma, and cancer immunotherapy could also be potential applications for these drugs.
📊 Hu Z, Tanji H, Jiang S, et al. Small-Molecule TLR8 Antagonists via Structure-Based Rational Design. Cell Chem Biol. 2018;25(10):1286-1291.e3.
🔗https://t.co/bk3F3hEqht
@alb_giraldo @ACR_Journals Which currently accessible repurposed drugs or natural agents target TLR8 even if non specifically?
A recent study investigated the role of Toll-like receptor 8 (#TLR8) in the development of #rheumatoid #arthritis (RA) and evaluated whether inhibiting TLR8 could be a promising new treatment approach.
Main Results:
◦ TLR8 is significantly overexpressed in RA patients and strongly correlates with disease activity (higher TLR8 levels = more severe disease).
◦ TLR8 drives key pathological processes in RA:
• Synovial hyperplasia: TLR8 promotes excessive proliferation of fibroblast-like synoviocytes, the cells responsible for destroying cartilage and bone in RA joints.
• Angiogenesis: TLR8 stimulates new blood vessel formation in the inflamed synovium (pannus formation).
• Inflammation: TLR8 activation strongly enhances the production of pro-inflammatory cytokines and mediators in RA synovial cells, endothelial cells (HUVECs), and immune cells (PBMCs from patients and RA monkey models).
◦ Mechanistic insight:
Upregulation and activation of TLR8 is a central driver that fuels the vicious cycle of synovial inflammation, hyperplasia, and angiogenesis in RA.
TLR8 inhibition is highly effective:
◦ Blocking TLR8 in vitro significantly reduced synoviocyte proliferation, angiogenesis, and inflammatory responses.
◦ In vivo, TLR8 antagonists showed clear therapeutic benefits in two different animal models:
▪Collagen-induced arthritis (CIA) mouse model
▪RA rabbit model
In both models, TLR8 inhibition led to:
• Reduced disease severity scores
• Decreased joint inflammation and swelling
• Protection against joint and bone damage
These findings indicate that TLR8 is a promising novel therapeutic target for the treatment of RA. TLR8 inhibitors could represent a new class of disease-modifying drugs, potentially offering benefits for patients who do not respond adequately to current therapies. This study provides robust evidence from human samples, in vitro RA models, and multiple animal models supporting the development of TLR8-targeted therapies for RA.
*Guo Y, Zhu T, Zhang X, et al. Toll-like receptor 8 is a therapeutic target in rheumatoid arthritis. Arthritis Rheumatol. Published online April 13, 2026.
🔗https://t.co/TAXwYTP19Y
Big thanks to Thomas Baumert, Melanie Urbanek-Quaing and @CornbergMarkus for the editorial at @Gut_BMJ!
https://t.co/k9gyQCt3RN
@TestoniResearch @FabienZoulim @ipcureb #HBV #TLR8 #Kupffer
Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease #TLR7 #TLR8 #MECFS #LongCovid
https://t.co/p0R4rgwSEi
Clementine is only female & 1 of only 9 children in world to be diagnosed w/ #TLR8 #genemutation. She’s also 1 of 2 to have it in every cell of their body.
Still can register online, anyone ages 18 to 55 in good health is eligible
https://t.co/MoEqfbOxdf
@KDKA #bonemarrow
#UPDATE: 8-mth-old Clementine Blackham’s mom tells me nearly 460 ppl got swabbed & signed up for National #BoneMarrow Registry at The Block Northway in @TownshipOfRoss today
She has an extremely rare #genemutation called #TLR8 & her only hope at surviving is a transplant
@KDKA
Just arrived!! Streamlight TLR-8 AG Flex. White LED with Green Laser! Come by the store and grab yours today!
#Streamlight
#TLR8
#FirearmLights
Just arrived!! Streamlight TLR-8 AG Flex. White LED with Green Laser! Come by the store and grab yours today!
#Streamlight
#TLR8
#FirearmLights
Activation of #TLR8 can elicit a robust immune response, critical for mounting productive anti-tumor and anti-viral responses, through a multi-pronged mechanism of action.
We are excited to share that Silverback has been recognized as the 2021 Best New Drug Developer by @World_ADC #TLR8 #HER2
@MrSteThompson @blink182 @BIGDaddyDigital Lol
They can certainly make a “vaccine” that lets cancer overtake your immune system.
It’s all about $$$.
Give them a “free” shot, reap the profits when they develop cancer.
#TLR8
Catch my talk at the upcoming #ACR #ACR2021 in the #InnateImmunity session!! See ya’ll there #Excited #TLR8 #Lupus #Anemia #Rheumatology
We are actively recruiting individuals for our ongoing #clinicaltrial evaluating SBT6050, a #HER2 directed #TLR8 ImmunoTAC® therapeutic, alone and in combination with pembrolizumab in patients with advanced HER2-expressing solid tumors. Learn more here: https://t.co/Cl6lELIASS
SARS-CoV-2-associated ssRNAs trigger inflammation and immunity via toll-like receptors https://t.co/7f36n8sM4J @biorxivpreprint @unibs_official @UniVerona @HUNIMED @QMUL @SapienzaRoma #Antibodies #Coronavirus #Cytokine #Genome #Pathology #Virus #COVID #TLR7 #TLR8
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