Ask about this productRelated genes to: SLC15A4 antibody
- Gene:
- SLC15A4 NIH gene
- Name:
- solute carrier family 15 member 4
- Previous symbol:
- -
- Synonyms:
- PHT1, PTR4
- Chromosome:
- 12q24.33
- Locus Type:
- gene with protein product
- Date approved:
- 2003-09-09
- Date modifiied:
- 2016-10-05
Related products to: SLC15A4 antibody
Related articles to: SLC15A4 antibody
- Nucleic acid sensing by endolysosomal Toll-like receptors is critically involved in systemic lupus erythematosus (SLE) and related autoimmune diseases. Downstream of TLR7, TLR8, and TLR9, the SLE-associated SLC15A4-TASL complex selectively mediates IRF5 activation, while being dispensable for NF-κB and MAPK pathways. Here, we show that the SLC15A4-TASL signaling axis is broadly required for disease development and pathogenesis across three complementary genetic SLE models, reflecting different etiologies. Genetic ablation of () and its paralogue () ameliorated or fully prevented autoimmune manifestations resulting from loss of function, respectively. Furthermore, SLC15A4-TASL complex deficiency was sufficient to protect from disease, including splenomegaly, immune activation, and autoantibody formation, driven by the patient-derived gain-of-function mutation, even in the presence of functional NF-κB and MAPK responses. Last, splenocyte transfer into lymphopenic -deficient mice demonstrated that protection extends to DNA-driven autoimmunity, in which TLR7 and TLR9 act redundantly, strongly supporting a B cell-intrinsic role. Notably, SLC15A4-TASL complex deficiency blunted the generation of pathogenic age-associated B cells in all three autoimmune models as well as in aged animals. Collectively, these data demonstrate the central role of the SLC15A4-TASL complex in SLE, supporting its potential as therapeutic target. - Source: PubMed
Publication date: 2026/09/01
Drobek AlesDelacrétaz MaevaVasilakou AlikiMonguió-Tortajada MartaBernaleau LéaDubois MaximeSisirak VanjaRebsamen Manuele - Salinity is a key environmental factor affecting the survival, growth, and reproduction of fish, and the euryhaline red tilapia (Oreochromis spp.) is an ideal model for investigating salinity adaptation mechanisms in fish. In this study, red tilapia (body weight 139.43 ± 41.74 g) were directly transferred from freshwater (control group, C) to water with a salinity of 15 ± 0.1‰ (experimental group, E) for 96 h of acute stress. Gill histological structure, physiological and biochemical parameters, and transcriptomic and metabolomic profiles were analyzed. The results showed that, compared with the 0 h group (control group), SOD activity was significantly elevated at all time points, GSH-Px activity was significantly elevated at 12-24 h, CAT activity was significantly elevated at 36-96 h, and MDA content was significantly increased at 12-48 h (P < 0.05). In gill tissue, slc15a4 expression first increased significantly, falling below the control level at 96 h, whereas cndp2 expression increased continuously and peaked at 96 h. Transcriptomic analysis identified a total of 1088 differentially expressed genes (339 up-regulated and 749 down-regulated), which were significantly enriched in focal adhesion, ECM-receptor interaction, the PI3K-Akt signaling pathway, glutathione metabolism, and the AMPK signaling pathway. Metabolomic analysis identified 250 differentially accumulated metabolites (135 up-regulated and 115 down-regulated), which were significantly enriched in β-alanine metabolism, ABC transporters and multiple metabolic pathways. Integrated multi-omics analysis further revealed that the differentially expressed genes and metabolites were jointly enriched in 12 pathways, including β-alanine metabolism, ABC transporters, neuroactive ligand-receptor interaction, and glycerophospholipid metabolism. In conclusion, β-alanine and arachidonic acid may be interconnected during salinity adaptation in red tilapia. - Source: PubMed
Publication date: 2026/08/22
An JianminMeng ZhichaoZhang YuxunYao XiaoliMa HuanchaoYadata Gazahegn WakjiraTong YannanZhao JinliangZhang JunlingZhao Yan - SLC15A4 is a member of the solute carrier superfamily that has been strongly linked to the pathogenesis of the auto-immune disease SLE. The endo-lysosomally localized SLC15A4 has traditionally been considered a proton-dependent histidine and peptide transporter, but has also been shown to facilitate TLR7, 8, and 9 induced IFN-alpha signaling in B cells and pDCs. New research has shown that SLC15A4 facilitates endo-lysosomal TLR signaling through a scaffolding interaction with a newly identified signal transducer, termed TASL. This interaction enables TLR7, 8, and 9 induced IRF5 activation, which is a crucial pathway in the pathogenesis of lupus. SLC15A4 is therefore an attractive target for the development of drugs for the treatment of SLE, and several small molecule SLC15A4 binders have now been reported which are capable of inhibiting TLR7, 8, or 9 signaling. This review summarizes the SLC15A4:TASL complex, its link to SLE, existing evidence for the transporter activity of SLC15A4, the current small molecule binders, and tools available for further drug discovery efforts. - Source: PubMed
Wilkinson Alex LPopat DillonSengmany KathySilva Miguel CCharlton Steven JLay Charles S - Oral cancer continues to pose a major health problem worldwide, characterized by few treatment options and an unfavorable prognosis. The solute carrier family 15 member 4 (SLC15A4) has been reported to be associated with immune responses regulation and tumor progression. This study purpose was to reveal the role of SLC15A4 in regulating Toll-like receptor 9 (TLR9) activation and the subsequent JAK/STAT signaling pathway in the context of oral cancer progression. - Source: PubMed
Publication date: 2026/07/09
Feng MeilingBayi SigulengDeji DemaHan TanaZhang Yulan - Endolysosomal Toll-like receptors (TLRs) 7-9 are critical mediators of antimicrobial immunity, but their dysregulation drives pathogenic inflammation in autoimmune diseases such as systemic lupus erythematosus (SLE). The endolysosomal solute carrier SLC15A4 is essential for TLR7-9-mediated cytokine production and is strongly linked to SLE susceptibility, yet our understanding of the precise mechanisms by which it coordinates innate immune signaling remains incomplete. Here, we identify a direct interaction between SLC15A4 and LAMTOR1, a core scaffold subunit of the lysosomal Ragulator complex, and show that is required for coupling endolysosomal TLR activation to mTORC1 and downstream inflammatory responses. Structural modeling and site-directed mutagenesis suggest that the α1 helix of LAMTOR1 engages the substrate-binding pocket of SLC15A4, and disruption of this interface broadly suppresses TLR7-9-mediated cytokine production. Notably, this interaction regulates mTOR activation, IRF5/7 signaling, and downstream transcriptional responses through stimulus-dependent mechanisms. These findings define a previously uncharacterized SLC15A4-LAMTOR1 signaling interface that coordinates endolysosomal TLR-mTOR coupling and shapes downstream cytokine output. - Source: PubMed
Publication date: 2026/06/09
Chiu Tzu-YuanHall Peter RoryLazar Daniel CKim Arthur SForli StefanoWard Andrew BTeijaro John RParker Christopher G