Proliferation and differentiation of CD4+ T cells induced by IL-27 in primary biliary cirrhosis

Abstract

Objective To investigate mechanisms for IL-27 induced proliferation and differentiation of peripheral blood CD4+ T cells in primary biliary cirrhosis (PBC).Methods Periperal blood CD4+ T cells were isolated from patients with PBC,chonic hepatitis B (CHB) and health controls (HCs).After IL-27 stimulation,proliferation ability of CD4+ T cells was evaluated by CCK-8 kit,and cytokines were analyzed by ELISA.Real-time PCR was employed to assay mRNA expression of T-bet and GATA3 in CD4+ T cells.p-STAT-1 and pSTAT-3 expression in CD4+ T cells were detected by Western blot.Results Enhanced proliferation of CD4+ T cells was found in all subjects after IL-27 stimulation.However,the proliferation ability in patients with PBC was greater than that in CHB and HCs ( P＜0.001 ).Levels of IL-2 and IFN-γ in supernatant from IL-27-incubated PBC blood CD4+ T cells were higher than that from CHB and HCs (P＜0.001 ).In normal situation,T-bet mRNA of CD4+ T cells in PBC group was higher than that in CHB group (P=0.007).Furthermore,after IL-27 stimulation,elevated T-bet mRNA expression and GATA3 inhibition were found in patients with PBC.High expression of p-STAT-1 and p-STAT-3 in blood CD4+ T cells were found in PBC,CHB and HCs after stimulation by IL-27.But their expression in patients with PBC were higher than those in patients with CHB and HCs.Conclusion Proliferation of blood CD4+ T cells could be induced by IL-27 in patients with PBC.The signaling pathways of p-STAT-1,p-STAT-3 were involved to induce Th1 immune response and related cytokines expression.This study implicated that IL-27 may play important roles in early inflammation damage in PBC. Key words: IL-27 ; Primary biliary cirrhosis; CD4 ; T lymphocyte