精氨酸酶
免疫病理学
免疫学
趋化因子
生物
髓样
免疫系统
离体
乙型肝炎病毒
T细胞
病毒
精氨酸
体内
生物化学
氨基酸
生物技术
作者
Laura J. Pallett,Upkar S. Gill,Alberto Quaglia,Linda V. Sinclair,Maria Jover‐Cobos,Anna Schurich,Kasha P. Singh,Niclas Thomas,Abhishek Das,Antony Chen,Giuseppe Fusai,Antonio Bertoletti,Doreen A. Cantrell,Patrick Kennedy,Nathan Davies,Muzlifah Haniffa,Mala K. Maini
出处
期刊:Nature Medicine
[Springer Nature]
日期:2015-05-11
卷期号:21 (6): 591-600
被引量:233
摘要
Pallett et al. report that myeloid derived suppressor cells expand, home to the liver, and inhibit T cell-mediated liver damage in chronic hepatitis B virus infection. Infection with hepatitis B virus (HBV) results in disparate degrees of tissue injury: the virus can either replicate without pathological consequences or trigger immune-mediated necroinflammatory liver damage. We investigated the potential for myeloid-derived suppressor cells (MDSCs) to suppress T cell–mediated immunopathology in this setting. Granulocytic MDSCs (gMDSCs) expanded transiently in acute resolving HBV, decreasing in frequency prior to peak hepatic injury. In persistent infection, arginase-expressing gMDSCs (and circulating arginase) increased most in disease phases characterized by HBV replication without immunopathology, whilst L-arginine decreased. gMDSCs expressed liver-homing chemokine receptors and accumulated in the liver, their expansion supported by hepatic stellate cells. We provide in vitro and ex vivo evidence that gMDSCs potently inhibited T cells in a partially arginase-dependent manner. L-arginine–deprived T cells upregulated system L amino acid transporters to increase uptake of essential nutrients and attempt metabolic reprogramming. These data demonstrate the capacity of expanded arginase-expressing gMDSCs to regulate liver immunopathology in HBV infection.
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