Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells
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 T Kennedy, Nathan A Davies, Muzlifah Haniffa & Mala K Maini
Nature Medicine 21, 591–600 (2015) doi:10.1038/nm.3856
Received
14 January 2015
Accepted
31 March 2015
Published online
11 May 2015
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. 作者: StephenW 时间: 2015-6-5 09:24
Regulation of immunopathology in hepatitis B virus infection
Silvia Piconese & Vincenzo Barnaba
In the liver there is a fine balance between immune surveillance of blood-borne infections and regulation of immunopathology. A new study identifies a role for granulocytic myeloid-derived suppressor cells in limiting T cell–mediated immunopathology in hepatitis B virus infection.