Tim-3 regulates inflammatory cytokine expression and Th17 cell response induced by monocytes from patients with chronic hepatitis B.

Tim-3 is expressed on monocytes/macrophages and is involved in the regulation of inflammatory responses. The aim of this study was to determine the effect of Tim-3 on inflammatory response triggered by peripheral monocytes from patients with chronic hepatitis B (CHB). Tim-3 expression on peripheral monocytes and frequency of Th17 cells in peripheral blood mononuclear cells (PBMCs) derived from CHB patients were detected. Followed by lipopolysaccharides (LPS) activation of circulating monocytes from CHB patients, expression of inflammatory cytokines including TNF-α，IL-1β and IL-6 were examined in the presence and absence of Galectin-9 which is the ligand for Tim-3. Subsequently, after purified CD4+T cells were cocultured with LPS-activated monocytes from CHB patients in the presence of anti-Tim-3 antibody, percentage of Th17 cells and production of IL-17 were measured. Tim-3 expression was significantly upregulated and closely correlated to the frequency of Th17 cells in patients with CHB. Expression of TNF-α，IL-1β and IL-6 increased significantly in monocytes stimulated with LPS and Galectin-9, compared to LPS stimulation alone. LPS-activated monocytes from CHB patients could drive differentiation of memory CD4+T cells to Th17 cells. However, under the blockade of Tim-3 signalling by anti-Tim-3 antibody, percentage of Th17 cells and production of IL-17 decreased significantly. Our results demonstrate that upregulated expression of Tim-3 on circulating monocytes accelerates inflammatory response by promoting production of inflammatory cytokines and Th17 responses in CHB.