biostudies-literatureKobayashi TMinistry of Education, Culture, Sports, Science and TechnologyNational Center for Global Health and MedicineMEXT | JST | Exploratory Research for Advanced Technologye2100295118https://www.ebi.ac.uk/biostudies/studies/S-EPMC8379930biostudies-literatureUnknown118(33)The amino acid and oligopeptide transporter Solute carrier family 15 member A4 (SLC15A4), which resides in lysosomes and is preferentially expressed in immune cells, plays critical roles in the pathogenesis of lupus and colitis in murine models. Toll-like receptor (TLR)7/9- and nucleotide-binding oligomerization domain-containing protein 1 (NOD1)-mediated inflammatory responses require SLC15A4 function for regulating the mechanistic target of rapamycin complex 1 (mTORC1) or transporting L-Ala-γ-D-Glu-meso-diaminopimelic acid, IL-12: interleukin-12 (Tri-DAP), respectively. Here, we further investigated the mechanism of how SLC15A4 directs inflammatory responses. Proximity-dependent biotin identification revealed glycolysis as highly enriched gene ontology terms. Fluxome analyses in macrophaProceedings of the National Academy of Sciences of the United States of AmericaSLC15A4 mediates M1-prone metabolic shifts in macrophages and guards immune cells from metabolic stress.PMC837993020H0535418K07056FY2010-FY205023S00117H0407018K16162Nguyen-Tien DGoda NShimabukuro-Demoto SSuzuki TUemura TKobayashi TDohmae NOkamura TTaguchi TSorimachi YUeki KSugiura YKato NKaryu HToyama-Sorimachi NTakubo KSuematsu MfalseSLC15A4 mediates M1-prone metabolic shifts in macrophages and guards immune cells from metabolic stress.The amino acid and oligopeptide transporter Solute carrier family 15 member A4 (SLC15A4), which resides in lysosomes and is preferentially expressed in immune cells, plays critical roles in the pathogenesis of lupus and colitis in murine models. Toll-like receptor (TLR)7/9- and nucleotide-binding oligomerization domain-containing protein 1 (NOD1)-mediated inflammatory responses require SLC15A4 function for regulating the mechanistic target of rapamycin complex 1 (mTORC1) or transporting L-Ala-γ-D-Glu-meso-diaminopimelic acid, IL-12: interleukin-12 (Tri-DAP), respectively. Here, we further investigated the mechanism of how SLC15A4 directs inflammatory responses. Proximity-dependent biotin identification revealed glycolysis as highly enriched gene ontology terms. Fluxome analyses in macropha2021-01-01T00:00:00Z2021 Aug2026-05-31T07:05:59.802Z2024-11-06T18:53:19.9ZS-EPMC83799303438531710.1073/pnas.2100295118