Effect of LncRNA XIST on Immune Cells of Primary Biliary Cholangitis

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.

lncRNA X‐inactive‐specific transcript is a potential biomarker related to changes in CD4+ T cell levels in systemic lupus erythematosus

“…29,30 She et al reported that high expression of the lncRNA XIST can stimulate the proliferation and differentiation of naive CD4 + T cells in female patients with primary biliary cholangitis (an autoimmune disease that predominantly affects females). 31 Therefore, similar to primary biliary cholangitis, XIST may promote the increase, overactivation, and differentiation of CD4 + T cells, leading to immune dysregulation and tissue damage in SLE. A limitation of this study is that we did not isolate NK cells and only detected the expression of XIST in the remaining cells (including NK cells and other types of immune cells), which showed no difference between SLE patients and healthy controls.…”

Roles of Non-Coding RNAs in Primary Biliary Cholangitis

“…Zhang et al (2013) wrote in his doctoral dissertation that the lncRNA AK053349 was increased in PBMC of PBC patients and positively correlated with the Mayo risk score, emphasizing its potential relevance to the pathogenesis of PBC and worthy of further study (Zhang et al, 2013). Another recent domestic study (She, 2020) found that the expression level of lncRNA XIST in NK cells and CD4 + T lymphocytes of PBC patients was significantly higher than that of healthy controls, and could be clearly located in the nucleus. The high expression of lncRNA XIST in Naïve CD4 + T cells of PBC patients can promote the proliferation of Naïve CD4 + T cells, stimulate the secretion of IFN-γ, IL-17, TGF-β and ROR-γ T cells, and increase the proportion of Th1 and Th7 cells, which led to the occurrence of PBC.…”

Maternal infection causes dysfunctional BCR signaling in male offspring due to aberrant Xist expression

“…6C), suggesting differential V(D)J recombination. Moreover, some of these genes have been connected with autoimmune disease (51), of which aberrant Xist is known to play a pivotal role (52)(53)(54). Overall, when comparing Xist positive cells to Xist negative cells in males from infected mothers, Xist positive cells downregulate multiple genes necessary for B cell function, such as Cd79a, Cd79b, Ebf1, Rag1, and Cd74 (Fig.…”