Browsing by Subject "Natural killer cells, Methylation"

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    DNMT1 silencing induces KIR2DL1/2/3 expression via methylation to alleviate graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Zhang, Ping; Yu, Shuling; Yan, Xiao; Zhu, Huiling; Sheng, Lixia; Zhang, Yi; Yang, Shujun; Ouyang, Guifang; Biología Celular e Histología
    Natural killer (NK) cells are the promoters in graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), while demethylation can regulate NK cell function. We explored the mechanism of demethylation regulating NK cell function to affect GVHD after allo-HSCT. BALB/c mice were transfused with C57BL/6 mouse-derived NK and bone marrow cells to establish GVHD models, followed by isolation and in vitro expansion of NK cells. NK cell purity, cytokine levels, proliferation, and cytokine-producing NK cell levels were measured via flow cytometry. KIR2DL1/2/3 methylation was tested by Methylation-specific polymerase chain reaction (MSP), with determination of mouse survival and GVHD scores. KIR2DL1/2/3 and DNMT1 expression was detected through qRT-PCR and/or western blot. Methylation levels were upregulated and KIR2DL1/2/3 expression was downregulated in GVHD mouse model-derived NK cells following IL-2 stimulation. DNMT1 silencing promoted KIR2DL1/2/3 expression, proliferation, and the secretion of Granzyme, Perforin, and Interferon-γ (IFN-γ) in C57BL/6 mouse-derived NK cells. DNMT1 silencing also enhanced mouse survival, reduced GVHD scores, promoted KIR2DL1/2/3 expression on the NK cell surface, and increased the secretion of Granzyme, Perforin, IFN-γ, and the number of cytokine-producing NK cells in the spleen, liver, and lung tissues of the models. Collectively, DNMT1 silencing induced KIR2DL1/2/3 expression in NK cells through reducing methylation to alleviate GVHD after allo-HSCT