HMGB1-induced autophagy: a new pathway to maintain Treg cell function during chronic hepatitis B virus infection

High-mobility group box-1 protein (HMGB1), as one of the well-known damage-associated molecular pattern molecules (DAMPs), is enriched in chronic hepatitis B virus (HBV) infection and has a context-dependent role in autophagy, a highly-conserved self-digestive process in response to environmental stress. Recent mouse studies indicate autophagy is highly active in regulatory T cells (Treg). Here, we evaluated spontaneous and induced autophagy of peripheral Treg cells from 98 patients with chronic hepatitis B (CHB), by measuring levels of lipidated form of microtubule-associated light chain 3 (LC3-II, marker for closed autophagosomes) and observing autophagic vacuoles with transmission electron microscope. No significant difference was found in spontaneous autophagy of either Treg or CD4+ naive cells when compared CHB patients with healthy subjects, apart from CHB-Treg showed significantly higher autophagic activity after activation by anti-CD3-CD28 beads. Besides, incubation of CHB-Treg cells with CHB-serum greatly maintained their autophagic behavior, which could be significantly diminished by block of HMGB1 with the neutralizing antibody. Further, we characterized time-and-dose dependent effects by recombinant HMGB1 protein on autophagy of CHB-Treg cells. We also documented a significant up-regulation of HMGB1 and its receptors (TLR4, RAGE) in both peripheral and intra-hepatic microenvironments of CHB patients. Moreover, the RAGE-ERK axis and rapamycin-sensitive components o...

Source: Clinical Science - January 11, 2017 Category: Biomedical Science Authors: Cheng, L.-s., Li, J., Liu, Y., Wang, F.-p., Wang, S.-q., She, W.-m., Wu, S.-d., Qi, X.-l., Zhou, Y.-p., Jiang, W. Tags: PublishAheadOfPrint Source Type: research