{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Potter SJ"],"funding":["NIDDK NIH HHS","NINDS NIH HHS","NIAMS NIH HHS"],"pagination":["1341745"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11099208"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15"],"pubmed_abstract":["Individuals with Kabuki syndrome present with immunodeficiency; however, how pathogenic variants in the gene encoding the histone-modifying enzyme lysine methyltransferase 2D (KMT2D) lead to immune alterations remain poorly understood. Following up on our prior report of KMT2D-altered integrin expression in B-cells, we performed targeted analyses of KMT2D's influence on integrin expression in T-cells throughout development (thymocytes through peripheral T-cells) in murine cells with constitutive- and conditional-targeted <i>Kmt2d</i> deletion. Using high-throughput RNA-sequencing and flow cytometry, we reveal decreased expression (both at the transcriptional and translational levels) of a cluster of leukocyte-specific integrins, which perturb aspects of T-cell activation, maturation, adhesion/localization, and effector function. H3K4me3 ChIP-PCR suggests that these evolutionary similar integrins are under direct control of KMT2D. KMT2D loss also alters multiple downstream programming/signaling pathways, including integrin-based localization, which can influence T-cell populations. We further demonstrated that KMT2D deficiency is associated with the accumulation of murine CD8<sup>+</sup> single-positive (SP) thymocytes and shifts in both human and murine peripheral T-cell populations, including the reduction of the CD4<sup>+</sup> recent thymic emigrant (RTE) population. Together, these data show that the targeted loss of <i>Kmt2d</i> in the T-cell lineage recapitulates several distinct features of Kabuki syndrome-associated immune deficiency and implicates epigenetic mechanisms in the regulation of integrin signaling."],"journal":["Frontiers in immunology"],"pubmed_title":["KMT2D regulates activation, localization, and integrin expression by T-cells."],"pmcid":["PMC11099208"],"funding_grant_id":["P30 DK078392","R03 NS133727","P30 AR070549"],"pubmed_authors":["Bjornsson HT","Stefan K","Potter SJ","Barski A","Kotliar M","Zhang L","Schafer C","Bodamer O","Simpson BN","Lindsley AW","Boukas L","Qu'd D","Wu Y"],"additional_accession":[]},"is_claimable":false,"name":"KMT2D regulates activation, localization, and integrin expression by T-cells.","description":"Individuals with Kabuki syndrome present with immunodeficiency; however, how pathogenic variants in the gene encoding the histone-modifying enzyme lysine methyltransferase 2D (KMT2D) lead to immune alterations remain poorly understood. Following up on our prior report of KMT2D-altered integrin expression in B-cells, we performed targeted analyses of KMT2D's influence on integrin expression in T-cells throughout development (thymocytes through peripheral T-cells) in murine cells with constitutive- and conditional-targeted <i>Kmt2d</i> deletion. Using high-throughput RNA-sequencing and flow cytometry, we reveal decreased expression (both at the transcriptional and translational levels) of a cluster of leukocyte-specific integrins, which perturb aspects of T-cell activation, maturation, adhesion/localization, and effector function. H3K4me3 ChIP-PCR suggests that these evolutionary similar integrins are under direct control of KMT2D. KMT2D loss also alters multiple downstream programming/signaling pathways, including integrin-based localization, which can influence T-cell populations. We further demonstrated that KMT2D deficiency is associated with the accumulation of murine CD8<sup>+</sup> single-positive (SP) thymocytes and shifts in both human and murine peripheral T-cell populations, including the reduction of the CD4<sup>+</sup> recent thymic emigrant (RTE) population. Together, these data show that the targeted loss of <i>Kmt2d</i> in the T-cell lineage recapitulates several distinct features of Kabuki syndrome-associated immune deficiency and implicates epigenetic mechanisms in the regulation of integrin signaling.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024","modification":"2026-06-01T08:06:30.509Z","creation":"2026-04-08T10:51:56.832Z"},"accession":"S-EPMC11099208","cross_references":{"pubmed":["38765012"],"doi":["10.3389/fimmu.2024.1341745"]}}