ArticleThe EMBO journal2022
The phagosomal solute transporter SLC15A4 promotes inflammasome activity via mTORC1 signaling and autophagy restraint in dendritic cells.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- The Pharmacology of the SLC15A4-TASL Complex, an Emerging Target for the Treatment of Lupus.Pharmacology research & perspectives · 2026Review
- Parkinson's disease-associated alterations in DNA methylation and hydroxymethylation in human brain.NPJ Parkinson's disease · 2025Article
- The lysosomal carrier SLC29A3 supports antibacterial signaling, and promotes autophagy by activating TRPML1 in murine dendritic cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Activation and regulation of NAIP/NLRC4 and NLRP3 inflammasomes during Salmonella infection: mechanisms and therapeutic implications.Molecular biology reports · 2025Review
- Development of conformation-selective antibodies targeting human SLC15A4.Nature communications · 2025Article
- Upregulated E26 Transformation-Specific Variant Transcription Factor 7 in Oral Squamous Cell Carcinoma: Clinicopathological Correlations and Immune Regulatory Mechanisms.World journal of oncology · 2025Article
- Regulation of dendritic cell biology by amino acids and their transporters.Frontiers in immunology · 2025Review
- Mycobacterium tuberculosis Utilizes Serine/Threonine Kinase PknF to Evade NLRP3 Inflammasome-driven Caspase-1 and RIPK3/Caspase-8 Activation in Murine Dendritic Cells.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Chemoproteomic development of SLC15A4 inhibitors with anti-inflammatory activity.Nature chemical biology · 2024Article
- Microbial sensing in the intestine.Protein & cell · 2023Review
- Oligopeptide/Histidine Transporter PHT1 and PHT2 - Function, Regulation, and Pathophysiological Implications Specifically in Immunoregulation.Pharmaceutical research · 2023Review
- A Non-Coding Variant inFrontiers in lupus · 2023Article
- Examining the Kinetics of Phagocytosis-Coupled Inflammasome Activation in Murine Bone Marrow-Derived Dendritic Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The phagosomal solute transporter SLC15A4 promotes inflammasome activity via mTORC1 signaling and autophagy restraint in dendritic cells.The EMBO journal · 2022Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Phagocytosis is the necessary first step to sense foreign microbes or particles and enables activation of innate immune pathways such as inflammasomes. However, the molecular mechanisms underlying how phagosomes modulate inflammasome activity are not fully understood. We show that in murine dendritic cells (DCs), the lysosomal histidine/peptide solute carrier transporter SLC15A4, associated with human inflammatory disorders, is recruited to phagosomes and is required for optimal inflammasome activity after infectious or sterile stimuli. Dextran sodium sulfate-treated SLC15A4-deficient mice exhibit decreased colon inflammation, reduced IL-1β production by intestinal DCs, and increased autophagy. Similarly, SLC15A4-deficient DCs infected with Salmonella typhimurium show reduced caspase-1 cleavage and IL-1β production. This correlates with peripheral NLRC4 inflammasome assembly and increased autophagy. Overexpression of constitutively active mTORC1 rescues decreased IL-1β levels and caspase1 cleavage, and restores perinuclear inflammasome positioning. Our findings support that SLC15A4 couples phagocytosis with inflammasome perinuclear assembly and inhibition of autophagy through phagosomal content sensing. Our data also reveal the previously unappreciated importance of mTORC1 signaling pathways to promote and sustain inflammasome activity.
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