Abstract
ObjectivePrimary biliary cholangitis (PBC) is an autoimmune disease with significant gender difference. X chromosome inactivation (XCI) plays important roles in susceptibility to diseases between genders. This work focuses on the differences of LncRNA XIST in several defined immune cells populations as well as its effects on naive CD4+ T cells proliferation and differentiation in patients with PBC.MethodsNKs, B cells, CD4+ T, and CD8+ T cells were separated by MicroBeads from peripheral blood mononuclear cells (PBMCs) of PBC patients and healthy control (HC). The expression levels of LncRNA XIST in these immune cells were quantified by qRT-PCR and their subcellular localized analyzed by FISH. Lentivirus were used to interfere the expression of LncRNA XIST, and CCK8 was used to detect the proliferation of naive CD4+ T cells in PBC patients. Finally, naive CD4+ T cells were co-cultured with the bile duct epithelial cells (BECs), and the effects of LncRNA XIST on the typing of naive CD4+ T cells and related cytokines were determined by qRT-PCR and ELISA.ResultsThe expression levels of LncRNA XIST in NKs and CD4+ T cells in PBC patients were significantly higher than those in HC, and were primarily located at the nucleus. LncRNA XIST could promote the proliferation of naive CD4+ T cells. When naive CD4+ T cells were co-cultured with BECs, the expressions of IFN-γ, IL-17, T-bet and RORγt in naive CD4+ T cells were decreased.ConclusionLncRNA XIST was associated with lymphocyte abnormalities in patients with PBC. The high expression of LncRNA XIST could stimulate proliferation and differentiation of naive CD4+ T cells, which might account for the high occurrence of PBC in female.
Highlights
Primary Biliary Cholangitis (PBC) is a female predominant autoimmune disease characterized by high titer of anti-mitochondrial antibodies (AMAs) and elevated Alkaline phosphatase (ALP) [1]
There was no significant difference between the immune cells of PBC patients and HC under normal electron microscopy, but there were some differences in the levels of XIST ex1 and XIST ex5 were examined by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR)
The expression of LncRNA XIST in CD4+ T cells and NK cells were significantly higher in PBC patients than that in HC (1.26 ± 0.09 vs 0.48 ± 0.19, 1.19 ± 1.23 vs 0.34 ± 0.31, p
Summary
Primary Biliary Cholangitis (PBC) is a female predominant autoimmune disease characterized by high titer of anti-mitochondrial antibodies (AMAs) and elevated Alkaline phosphatase (ALP) [1]. The incidence ratio of male to female is 1:9 [2]. X chromosome is the chromosome with the highest density of immune-related genes. In order to balance the immune system, a chromosome will be LncRNA XIST Effects CD4+T Cells permanently inactivated randomly in female development [3]. The association of X-chromosome inactivation (XCI) and inflammatory diseases implicates its significance in the gender predominance in autoimmunity [4–6]. LncRNA XIST as a critical factor for XCI based on its location within the X-inactivation centre (XIC) and its unique expression pattern that is completely female-specific in adult somatic cells [7]. LncRNA XIST engages with proteins in a modular and developmentally controlled manner to coordinate chromatin spreading and silencing [8]
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