The role of intrahepatic B cells in non-alcoholic fatty liver disease through secretion of pro-inflammatory cytokines and regulation of intrahepatic T cells

Abstract

Aims

To investigate the alterations and functions of B cells, especially the intrahepatic B (IHB) cells in high-fat diet (HFD) induced non-alcoholic fatty liver disease (NAFLD).

Methods

C57BL/6 J mice were induced NAFLD using 16-week HFD. Flow cytometry was used to analyze B cells and T cells in different tissues and co-culture system. Real-time PCR and immunofluorescence staining assays were applied to investigate cytokines expressions in livers, intrahepatic lymphocytes and IHB cells. CD4+ intrahepatic T (IHT) cells and IHB cells were enriched by magnetic-activated cell sorting method and cultured in vitro. The cytokines and immunoglobulin levels in plasma, cultural supernatants and liver homogenates were monitored with cytometric beads array or multiplex immunoassay.

Results

In the NAFLD group, IHB cells increased from 25.86 ± 2.41% to 30.12 ± 2.98% in the intrahepatic lymphocytes and expressed higher mRNA levels of IL-6 and TNF-α in vivo while secreted more IL-6 and TNF-α under lipopolysaccharide (LPS) stimulation in vitro. Also, IgG2a was higher in the plasma, liver homogenates as well as the culture supernatants of IHB cells with LPS and anti-CD40/IgM stimulation in the NAFLD group. Moreover, IHB cells enhanced the activation of CD4+ IHT cells and promoted the differentiation into Th1 cells, without influencing the proliferation in vitro in the NAFLD group.

Conclusions

The present findings demonstrate the strong and obvious evidence of IHB cells involved in NAFLD through both inducing the secretion of IL-6, TNF-α and IgG2a, and enhancing the activation of CD4+ IHT cells and their differentiation into Th1 cells.

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