Controlling inflammation can alleviate various diseases including immune-mediated, lifestyle-related, and neurodegenerative diseases, and thus developing novel therapeutic strategies to control prolonged and harmful inflammation are urgently needed.
The endolysosome system acts as a signaling hub where various nodes converge, and plays a pivotal role in inflammatory responses. Solute carrier family 15 member 3 (SLC15A3) and member 4 (SLC15A4) are endolysosome-resident amino acid transporters that are preferentially expressed in immune cells. The loss of either transporter causes the perturbation of endolysosome-dependent signaling events including inflammatory and metabolic signaling mediated by TLRs, NOD1/2, mTORC1 and AMPK, resulting in the alleviation of multiple inflammatory diseases such as systemic lupus erythematosus, colitis, diffuse alveolar hemorrhage, and fibrosis.
In this seminar, I will show our recent observations that SLC15A4 plays a critical role in M1-prone metabolic shift in macrophages and guards immune cells from metabolic stress. SLC15A4 mediates coupling between glycolysis and TCA cycle by controlling pyruvate dehydrogenase activity, and SLC15A4 loss causes the impairment of macrophage metabolic adaptation to environmental cue. I will also show our up-to-date data concerning the novel therapeutic strategy of lung fibrosis based on our new findings on the roles of SLC15A3 transporter. Considering the broad effects of SLC15A3/A4-deficiency on inflammatory and metabolic signals, these transporters are promising therapeutic targets for multiple inflammatory diseases.
Lysosomal amino acid transporters integrate inflammatory and metabolic signaling in macrophages
|講師||反町 典子（Dr. Noriko Toyama-Sorimachi）|
|所属・職名||国立国際医療研究センター研究所 分子炎症制御プロジェクト・プロジェクト長 (Project Director, Department of Molecular Immunology and Inflammation, Research Institute, National Center for Global Health and Medicine)|
|演題||Lysosomal amino acid transporters integrate inflammatory and metabolic signaling in macrophages|
|世話人||主たる世話人：COBAN Cevayir（Division of Malaria Immunology）
ISHII Ken （Division of Vaccine Science）