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Role of intrahepatic B cells in non‐alcoholic fatty liver disease by secreting pro‐inflammatory cytokines and regulating intrahepatic T cells
Author(s) -
Zhang Feng,
Jiang Wei Wei,
Li Xia,
Qiu Xin Yun,
Wu Zhe,
Chi Yu Jing,
Cong Xu,
Liu Yu Lan
Publication year - 2016
Publication title -
journal of digestive diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 51
eISSN - 1751-2980
pISSN - 1751-2972
DOI - 10.1111/1751-2980.12362
Subject(s) - fatty liver , cd40 , tumor necrosis factor alpha , flow cytometry , peripheral blood mononuclear cell , lipopolysaccharide , cytokine , medicine , endocrinology , immunology , microbiology and biotechnology , biology , in vitro , biochemistry , cytotoxic t cell , disease
Objective To investigate the alterations and functions of intrahepatic B (IHB) cells in non‐alcoholic fatty liver disease (NAFLD) model induced by high‐fat diet (HFD). Methods C57BL/6 J mice were fed with HFD for 16 weeks to induce NAFLD. Flow cytometry was used to analyze lymphocytes from liver, spleen and peripheral blood mononuclear cells (PBMC). Real‐time polymerase chain reaction and immunofluorescence stain were applied to investigate cytokine expression in the intrahepatic lymphocytes and IHB cells. CD4 + intrahepatic T (IHT) cells and IHB cells were enriched by a magnetic‐activated cell sorting method and cultured in vitro . The cytokines and immunoglobulin (Ig) levels in the plasma, cultural supernatants and liver homogenates were monitored with cytometric bead arrays or multiplex immunoassays. Results The percentage of IHB cells in CD45 + cells was significantly higher in the NAFLD group than in the control group ( P < 0.05). IHB cells expressed higher levels of interleukin (IL)‐6 and tumor necrosis factor (TNF)‐α in the NAFLD group, and produced higher levels of IL‐6 and TNF‐α under the stimulation of lipopolysaccharide (LPS) than the control group. IgG2a levels were higher in the plasma, liver homogenates and the culture supernatants of IHB cells after stimulated by LPS and anti‐CD40/IgM in the NAFLD group than in the control group. Moreover, IHB cells enhanced the activation of CD4 + IHT cells and promoted the differentiation into T helper (Th) 1 cells in the NAFLD group. Conclusion IHB cells might be involved in NAFLD both by inducing the secretion of IL‐6, TNF‐α and IgG2a and by enhancing the activation of CD4 + IHT cells and their differentiation into Th1 cells.