Long Non-Coding RNA NEAT1 Enhances Histone Methylation Through Regulating MLL5-Mediated Foxp3 Expression in Tuberculosis

Abstract

Backgrounds: Tuberculosis (TB) is a leading infectious disease and cause of death worldwide. Abnormal expression of long non-coding RNAs (lncRNAs) has been demonstrated in a number of immune cells in TB patients, indicating that lncRNAs may be involved in immune regulation during TB. In this study, we aim to explore the effects of nuclear enriched abundant transcript 1 (NEAT1) on immunity in regulatory T (Treg) cells from a mouse model of TB. Methods: After TB bacteria inoculation, pathological changes in the lung of TB mice occurred with increased neutrophils and macrophages. The expression of NEAT1, MLL5 and Foxp3 was measured and their role in TB was evaluated with GapmeR or siRNA interference in Treg cells. NEAT1 was highly expressed in the nucleus of Treg cells from TB mice. NEAT1 interacted with MLL5 to enhance the binding of H3K4me3 to the Foxp3 promoter in Treg cells from TB mice. Findings: Proportions of CD3, CD3+CD4+ and CD3+CD8+ cells, IFN-γ and IgG levels were decreased in Treg cells from TB mice. NEAT1 or MLL5 silencing increased proportions of CD3, CD3+CD4+ and CD3+CD8+ cells and Treg cell proliferation. On the other hand, NEAT1 or MLL5 silencing increased the levels of IFN-γ, IL-10, IL-17, IL-6, IL-1β, IL-9 and reduced immunosuppressive effect of Treg cells from TB mice. Interpretation: Taken together, this study demonstrated that NEAT1 may be involved in TB progression via MLL5-mediated demethylation of H3K4me3 in the Foxp3 promoter region in Treg cells. Funding: This study was supported by National Natural Science Foundation of China (No. U1404814). Declaration of Interest: None Ethical Approval: The study was approved by the Animal Ethics Committee of The First Affiliated Hospital of Zhengzhou University. All animal experiments were carried out in accordance with the Guide for the Care and Use of Laboratory Animals provided by the National Institute of Health.