ArticleProceedings of the National Academy of Sciences of the United States of America2022
The solute carrier SLC15A4 is required for optimal trafficking of nucleic acid-sensing TLRs and ligands to endolysosomes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- 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
- TLR7 in systemic lupus erythematosus: genetics and emerging therapies.Nature reviews. Rheumatology · 2026Review
- The Pharmacology of the SLC15A4-TASL Complex, an Emerging Target for the Treatment of Lupus.Pharmacology research & perspectives · 2026Review
- SLC15A3-mediated dipeptide metabolism confers antimetabolite resistance in lymphoma via mTORC1 activation.The Journal of clinical investigation · 2026Article
- Heterodimerization with signaling-inert TLR8b converts TLR8a from proviral to antiviral sensor in Ctenopharyngodon idella.Cell communication and signaling : CCS · 2026Article
- Pathogen-specific immune responses might underlie divergent outcomes of coronavirus and influenza infection in the natural porcine host.Communications biology · 2026Article
- Renal macrophage TLR7 signaling in lupus nephritis: from pathogenic mechanisms to therapeutic opportunities.Frontiers in immunology · 2026Review
- Parkinson's disease-associated alterations in DNA methylation and hydroxymethylation in human brain.NPJ Parkinson's disease · 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 TLR7/9 adaptors TASL and TASL2 mediate IRF5-dependent antiviral responses and autoimmunity in mouse.Nature communications · 2025Article
- Defective endomembrane dynamics in Rab27a deficiency impairs nucleic acid sensing and cytokine secretion in immune cells.Cell reports · 2024Article
- Chemoproteomic development of SLC15A4 inhibitors with anti-inflammatory activity.Nature chemical biology · 2024Article
- Orphan lysosomal solute carrier MFSD1 facilitates highly selective dipeptide transport.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Endosomal Toll-Like Receptors as Therapeutic Targets for Autoimmune Diseases.Advances in experimental medicine and biology · 2024Article
- TLR7 neo-functionalizes to sense dsRNA and trigger antiviral and antibacterial immunity in non-tetrapod vertebrates.iScience · 2023Article
- Proton-Coupled Oligopeptide Transport (Slc15) in the Brain: Past and Future Research.Pharmaceutical research · 2023Review
- Understanding nucleic acid sensing and its therapeutic applications.Experimental & molecular medicine · 2023Review
- A conformation-locking inhibitor of SLC15A4 with TASL proteostatic anti-inflammatory activity.Nature communications · 2023Article
- Methotrexate suppresses psoriatic skin inflammation by inhibiting muropeptide transporter SLC46A2 activity.Immunity · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
A function-impairing mutation (feeble) or genomic deletion of SLC15A4 abolishes responses of nucleic acid–sensing endosomal toll-like receptors (TLRs) and significantly reduces disease in mouse models of lupus. Here, we demonstrate disease reduction in homozygous and even heterozygous Slc15a4 feeble mutant BXSB male mice with a Tlr7 gene duplication. In contrast to SLC15A4, a function-impairing mutation of SLC15A3 did not diminish type I interferon (IFN-I) production by TLR-activated plasmacytoid dendritic cells (pDCs), indicating divergence of function between these homologous SLC15 family members. Trafficking to endolysosomes and function of SLC15A4 were dependent on the Adaptor protein 3 (AP-3) complex. Importantly, SLC15A4 was required for trafficking and colocalization of nucleic acid–sensing TLRs and their ligands to endolysosomes and the formation of the LAMP2+VAMP3+ hybrid compartment in which IFN-I production is initiated. Collectively, these findings define mechanistic processes by which SLC15A4 controls endosomal TLR function and suggest that pharmacologic intervention to curtail the function of this transporter may be a means to treat lupus and other endosomal TLR-dependent diseases.
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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.