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Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells

Pallett, LJ; Gill, US; Quaglia, A; Sinclair, LV; Jover-Cobos, M; Schurich, A; Singh, KP; ... Maini, MK; + view all (2015) Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells. Nature Medicine , 21 (6) pp. 591-600. 10.1038/nm.3856. Green open access

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Abstract

© 2015 Nature America, Inc. All rights reserved. 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.

Type: Article
Title: Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nm.3856
Publisher version: http://dx.doi.org/10.1038/nm.3856
Language: English
Additional information: © 2015 Nature America, Inc. All rights reserved.
Keywords: Hepatitis B, Immune tolerance, Innate immune cells
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: https://discovery.ucl.ac.uk/id/eprint/1473049
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