Methamphetamine(METH)is a highly addictive psychostimulant that causes physical and psychological damage and immune system disorder,especially in the liver which contains a significant number of immune cells.Dopamine,...Methamphetamine(METH)is a highly addictive psychostimulant that causes physical and psychological damage and immune system disorder,especially in the liver which contains a significant number of immune cells.Dopamine,a key neurotransmitter in METH addiction and immune regulation,plays a crucial role in this process.Here,we developed a chronic METH administration model and conducted single-cell RNA sequencing(scRNA-seq)to investigate the effect of METH on liver immune cells and the involvement of dopamine receptor D1(DRD1).Our findings reveal that chronic exposure to METH induces immune cell identity shifts from IFITM3þmacrophage(Mac)and CCL5þMac to CD14þMac,as well as from FYNþCD4þT effector(Teff),CD8þT,and natural killer T(NKT)to FOSþCD4þT and RORαþgroup 2 innate lymphoid cell(ILC2),along with the suppression of multiple functional immune pathways.DRD1 is implicated in regulating certain pathways and identity shifts among the hepatic immune cells.Our results provide valuable insights into the development of targeted therapies to mitigate METHinduced immune impairment.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.81770798)the Natural Science Foundation of Shaanxi Province(Grant No.2020JQ-083).
文摘Methamphetamine(METH)is a highly addictive psychostimulant that causes physical and psychological damage and immune system disorder,especially in the liver which contains a significant number of immune cells.Dopamine,a key neurotransmitter in METH addiction and immune regulation,plays a crucial role in this process.Here,we developed a chronic METH administration model and conducted single-cell RNA sequencing(scRNA-seq)to investigate the effect of METH on liver immune cells and the involvement of dopamine receptor D1(DRD1).Our findings reveal that chronic exposure to METH induces immune cell identity shifts from IFITM3þmacrophage(Mac)and CCL5þMac to CD14þMac,as well as from FYNþCD4þT effector(Teff),CD8þT,and natural killer T(NKT)to FOSþCD4þT and RORαþgroup 2 innate lymphoid cell(ILC2),along with the suppression of multiple functional immune pathways.DRD1 is implicated in regulating certain pathways and identity shifts among the hepatic immune cells.Our results provide valuable insights into the development of targeted therapies to mitigate METHinduced immune impairment.
