Department of Molecular Immunology and Inflammation, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, Japan.
Int Immunol. 2021 Nov 25;33(12):853-858. doi: 10.1093/intimm/dxab069.
Controlling inflammation can alleviate immune-mediated, lifestyle-related and neurodegenerative diseases. The endolysosome system plays critical roles in inflammatory responses. Endolysosomes function as signal transduction hubs to convert various environmental danger signals into gene expression, enabling metabolic adaptation of immune cells and efficient orchestration of inflammation. Solute carrier family 15 member A3 (SLC15A3) and member A4 (SLC15A4) are endolysosome-resident amino acid transporters that are preferentially expressed in immune cells. These transporters play essential roles in signal transduction through endolysosomes, and the loss of either transporter can alleviate multiple inflammatory diseases because of perturbed endolysosome-dependent signaling events, including inflammatory and metabolic signaling. Here, we summarize the findings leading to a proof-of-concept for anti-inflammatory strategies based on targeting SLC15 transporters.
控制炎症可以减轻免疫介导的、与生活方式相关的和神经退行性疾病。内溶酶体系统在炎症反应中起着关键作用。内溶酶体充当信号转导枢纽，将各种环境危险信号转化为基因表达，使免疫细胞能够进行代谢适应，并有效地协调炎症反应。溶质载体家族 15 成员 A3（SLC15A3）和成员 A4（SLC15A4）是内溶酶体驻留的氨基酸转运体，在免疫细胞中优先表达。这些转运体在通过内溶酶体的信号转导中发挥重要作用，由于内溶酶体依赖性信号事件的紊乱，任何一种转运体的缺失都可以减轻多种炎症性疾病，包括炎症和代谢信号。在这里，我们总结了导致基于靶向 SLC15 转运体的抗炎策略的概念验证的发现。
