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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

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dc.contributor.authorZhang, Ping
dc.contributor.authorYu, Shuling
dc.contributor.authorYan, Xiao
dc.contributor.authorZhu, Huiling
dc.contributor.authorSheng, Lixia
dc.contributor.authorZhang, Yi
dc.contributor.authorYang, Shujun
dc.contributor.authorOuyang, Guifang
dc.contributor.departmentBiología Celular e Histologíaes
dc.date.accessioned2025-07-21T10:18:10Z
dc.date.available2025-07-21T10:18:10Z
dc.date.issued2025
dc.description.abstractNatural 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-HSCTes
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dc.format.extent11es
dc.identifier.citationHistology and Histopathology Vol. 40, nº07 (2025)
dc.identifier.doihttps://doi.org/10.14670/HH-18-818
dc.identifier.issn0213-3911
dc.identifier.issn1699-5848
dc.identifier.urihttp://hdl.handle.net/10201/157581
dc.languageenges
dc.publisherUniversidad de Murcia, Departamento de Biologia Celular e Histiologiaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectDNA methyltransferasees
dc.subjectKiller cell immunoglobulin like receptores
dc.subjectTwo Ig domains and long cytoplasmic tail 1/2/3es
dc.subjectNatural killer cells, Methylationes
dc.subjectGraft versus host diseasees
dc.subjectAllogeneic hematopoietic stem cell transplantationes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleDNMT1 silencing induces KIR2DL1/2/3 expression via methylation to alleviate graft-versus-host disease after allogeneic hematopoietic stem cell transplantationes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.40, nº7 (2025)