Hepatitis B virus X protein modulates renal tubular epithelial cell-induced T-cell and macrophage responses.

Renal tubular epithelial cells (RTECs) have an active role in renal inflammation, functioning as antigen-presenting cells as they constitutively express major histocompatibility complex-II and co-stimulatory molecules that can activate T cells and macrophages. Previous studies indicate that inflammatory cell infiltration and tubulointerstitial fibrosis are present in renal biopsies from Hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN) patients. We hypothesized that disorder RTECs may be involved in the progression of HBV-GN. Here, we measured renal function and inflammatory cells infiltration in C57BL/6J-TgN mice, and data showed that in C57BL/6J-TgN mice HBV x protein (HBx) mainly deposited in RTECs, and CD4(+) T cells and macrophages infiltrated into the interstitium. In vitro HBx upregulated CD40 expression in RTECs. In HK-2/CD4(+) T cells co-culture system, we found that HBx-stimulated HK-2 cells could activate CD4(+) T cells, promote their proliferation, and lead to an imbalance of interleukin (IL)-4 and interferon-γ. In HK-2/macrophages co-culture system, we found that HBx-stimulated HK-2 cells also increased macrophage adherent capacity and promoted MCP-1 and tumor necrosis factor-α and IL-1β secretion. These immune dysfunction may contribute to the pathogenesis of HBV-GN.