ArticleNature communications2023
A conformation-locking inhibitor of SLC15A4 with TASL proteostatic anti-inflammatory activity.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- The SLC15A4-TASL complex is essential for lupus development in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- The Pharmacology of the SLC15A4-TASL Complex, an Emerging Target for the Treatment of Lupus.Pharmacology research & perspectives · 2026Review
- The adaptor protein TASL is required for age-related B cell emergence and lupus-like disease development in mice.PLoS biology · 2026Article
- Article
- Allosteric modulation of the solute carrier transporter SLC39A8 potentiates manganese and cadmium uptake.The Journal of clinical investigation · 2025Article
- TLR-induced STK25 activation promotes IRF5-mediated inflammation.Life science alliance · 2025Article
- METTL3/ALKBH5-Mediated N6-Methyladenosine Modification Drives Macrophage M1 Polarization via the SLC15A3-TASL-IRF5 Signaling Axis in Psoriasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Role of Solute Carriers in the Metabolic Reprogramming of Skin Diseases.Clinical reviews in allergy & immunology · 2025Review
- Development of conformation-selective antibodies targeting human SLC15A4.Nature communications · 2025Article
- Nucleic acid triggers of autoimmunity and autoinflammation.Current opinion in immunology · 2025Review
- CCDC134 controls TLR biogenesis through the ER chaperone Gp96.The Journal of experimental medicine · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- The TLR7/9 adaptors TASL and TASL2 mediate IRF5-dependent antiviral responses and autoimmunity in mouse.Nature communications · 2025Article
- Cytosolic delivery of innate immune agonists.Trends in immunology · 2024Review
- ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches.Pharmaceuticals (Basel, Switzerland) · 2024Review
- New approaches to the control of chronic inflammatory diseases with a focus on the endolysosomal system of immune cells.International immunology · 2024Review
- The Role of ABCB1, ABCG2, and SLC Transporters in Pharmacokinetic Parameters of Selected Drugs and Their Involvement in Drug-Drug Interactions.Membranes · 2024Review
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Systemic lupus erythematosus genetics: insights into pathogenesis and implications for therapy.Nature reviews. Rheumatology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
Dysregulation of pathogen-recognition pathways of the innate immune system is associated with multiple autoimmune disorders. Due to the intricacies of the molecular network involved, the identification of pathway- and disease-specific therapeutics has been challenging. Using a phenotypic assay monitoring the degradation of the immune adapter TASL, we identify feeblin, a chemical entity which inhibits the nucleic acid-sensing TLR7/8 pathway activating IRF5 by disrupting the SLC15A4-TASL adapter module. A high-resolution cryo-EM structure of feeblin with SLC15A4 reveals that the inhibitor binds a lysosomal outward-open conformation incompatible with TASL binding on the cytoplasmic side, leading to degradation of TASL. This mechanism of action exploits a conformational switch and converts a target-binding event into proteostatic regulation of the effector protein TASL, interrupting the TLR7/8-IRF5 signaling pathway and preventing downstream proinflammatory responses. Considering that all components involved have been genetically associated with systemic lupus erythematosus and that feeblin blocks responses in disease-relevant human immune cells from patients, the study represents a proof-of-concept for the development of therapeutics against this disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.