Effects of T cell immunoglobulin and mucin domain-containing molecule-3 signaling molecule on human monocyte-derived dendritic cells with hepatitis B virus surface antigen stimulation in vitro

Abstract

The aim of the present study was to investigate the in vitro effects of hepatitis B virus surface antigen (HBsAg) on the immune function of human monocyte-derived dendritic cells (MD‑DCs), and the moderating role of T cell immunoglobulin and mucin domain‑containing molecule‑3 (Tim‑3) signaling molecule. The monocytes, obtained from healthy adult peripheral blood, were incubated with recombinant human granulocyte‑macrophage colony‑stimulating factor and interleukin (IL)‑4 to induce DCs. DC‑associated cell markers were detected using flow cytometry. MD‑DCs were treated with HBsAg (5 µg/ml) in vitro for 48 h and subsequently, cell markers, lymphocyte stimulatory capacity, signaling protein and downstream cytokines were assessed. In addition, a Tim‑3 monoclonal antibody was used to inhibit the Tim‑3 signaling pathway, and subsequently the immune responses of MD‑DCs to HBsAg stimulation were determined using the aforementioned method. The cell phenotype expressions of MD‑DCs were all significantly increased with cluster of differentiation (CD)11c at 70.09±0.57%, human leukocyte antigen‑DR at 79.83±2.12%, CD80 at 48.33±7.34% and CD86 at 44.21±5.35%. The treatment of MD‑DCs with HBsAg resulted in a CD80 and CD86 enhanced expression, enhanced lymphocyte stimulatory capacity, upregulated expression of Tim‑3 and nuclear factor‑κB (NF‑κB), as well as enhanced cytokine secretion of IL‑6, IL‑10 and interferon (IFN)‑γ. However, a reduced immune response of MD‑DCs in response to HBsAg stimulation was observed when the Tim‑3 signaling pathway was inhibited prior to stimulation. The expression of NF‑κB was decreased and the cytokine secretion level of IL‑6, IL‑10 and IFN‑γ were downregulated. The treatment with HBsAg in vitro resulted in an enhanced immune response of MD‑DCs, which may be positively regulated by the Tim-3 signaling molecule.

Tim-3 inhibits macrophage control of Listeria monocytogenes by inhibiting Nrf2

“…During infection, Tim-3 expression has been reported to be upregulated on macrophages/monocytes and this inhibits their activation 11 12 . The physiopathological role of Tim-3 on T cells has been widely investigated 13 .…”

Expression of the Tim3‐galectin‐9 axis is altered in drug‐induced maculopapular exanthema

“…However, these levels were lower during the resolution phase. Tim3 has been described as an activation and maturation marker of natural killer and DCs ; thus, this increase suggests that the drug is able to selectively activate DCs in allergic patients. On the other hand, the production of Gal9 by moDCs in vitro is reduced in patients compared to controls and, although drug stimulation increased its release, its levels were still lower than those observed in healthy subjects.…”