HBx promotes glomerular podocyte-induced immune cell responses

Area of Science:

• Nephrology
• Immunology
• Virology

Background:

• Podocytes, crucial renal cells, can act as antigen-presenting cells (APCs) under inflammation, potentially causing immune-mediated kidney injury.
• Hepatitis B virus-associated glomerulonephritis (HBV-GN) involves podocytes as targets, with observed inflammatory cell infiltration and tissue damage.
• The specific role of podocyte immune dysregulation in HBV-GN pathogenesis remains largely unexplored.

Purpose of the Study:

• To investigate the role of podocyte immune disorder in the pathogenesis of hepatitis B virus-associated glomerulonephritis (HBV-GN).
• To explore the impact of the hepatitis B virus X protein (HBx) on podocyte immune function and its interaction with immune cells.

Main Methods:

• Assessed renal function and inflammatory cell infiltration in hepatitis B virus transgenic (HBV-Tg) mice.
• Utilized *in vitro* co-culture systems of podocytes with CD4+ T cells or macrophages.
• Quantified protein expression (HBx, CD4, CD68) via immunohistochemistry and immune markers (MHC-II, CD40, CD40L) via immunofluorescence and flow cytometry; measured inflammatory factors using ELISA.

Main Results:

• HBV-Tg mice exhibited impaired renal function, increased HBx expression, and glomerular immune cell infiltration.
• Podocytes in HBV-Tg mice showed upregulated MHC-II and CD40; CD4+ T cells displayed increased CD40L.
• *In vitro*, HBx-induced podocytes promoted CD4+ T cell activation, skewed cytokine balance (IFN-γ/IL-4), enhanced macrophage adhesion, and increased pro-inflammatory mediator release.

Conclusions:

• Podocyte immune dysregulation, particularly mediated by HBx, plays a significant role in the pathogenesis of HBV-GN.
• HBx-expressing podocytes can directly activate T cells and promote inflammatory responses involving macrophages.
• These findings identify podocyte immune dysfunction as a critical factor in HBV-GN development.