dc.contributor.author |
Potter, Sarah J. |
dc.contributor.author |
Zhang, Li |
dc.contributor.author |
Kotliar, Michael |
dc.contributor.author |
Wu, Yuehong |
dc.contributor.author |
Schafer, Caitlin |
dc.contributor.author |
Stefan, Kurtis |
dc.contributor.author |
Boukas, Leandros |
dc.contributor.author |
Qu’d, Dima |
dc.contributor.author |
Bodamer, Olaf |
dc.contributor.author |
Simpson, Brittany N. |
dc.contributor.author |
Barski, Artem |
dc.contributor.author |
Lindsley, Andrew W. |
dc.contributor.author |
Björnsson, Hans Tómas |
dc.date.accessioned |
2024-06-06T01:04:11Z |
dc.date.available |
2024-06-06T01:04:11Z |
dc.date.issued |
2024-05-03 |
dc.identifier.citation |
Potter , S J , Zhang , L , Kotliar , M , Wu , Y , Schafer , C , Stefan , K , Boukas , L , Qu’d , D , Bodamer , O , Simpson , B N , Barski , A , Lindsley , A W & Björnsson , H T 2024 , ' KMT2D regulates activation, localization, and integrin expression by T-cells ' , Frontiers in Immunology , vol. 15 , 1341745 , pp. 1341745 . https://doi.org/10.3389/fimmu.2024.1341745 |
dc.identifier.issn |
1664-3224 |
dc.identifier.other |
223202174 |
dc.identifier.other |
cf316a08-2202-4fb7-844f-39d3d5ba9ff2 |
dc.identifier.other |
85193471794 |
dc.identifier.other |
38765012 |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/4941 |
dc.description |
Publisher Copyright: Copyright © 2024 Potter, Zhang, Kotliar, Wu, Schafer, Stefan, Boukas, Qu’d, Bodamer, Simpson, Barski, Lindsley and Bjornsson. |
dc.description.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 Kmt2d 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+ single-positive (SP) thymocytes and shifts in both human and murine peripheral T-cell populations, including the reduction of the CD4+ recent thymic emigrant (RTE) population. Together, these data show that the targeted loss of Kmt2d 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. |
dc.format.extent |
20 |
dc.format.extent |
6117366 |
dc.format.extent |
1341745 |
dc.language.iso |
en |
dc.relation.ispartofseries |
Frontiers in Immunology; 15() |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Lífefna- og sameindalíffræði |
dc.subject |
integrin switching |
dc.subject |
Itgal |
dc.subject |
Itgb7 |
dc.subject |
Kabuki syndrome (KS) |
dc.subject |
KS1-associated immune deficiency (KSAID) |
dc.subject |
recent thymic emigrant (RTE) |
dc.subject |
thymocyte |
dc.subject |
Hematologic Diseases |
dc.subject |
Humans |
dc.subject |
Integrins/metabolism |
dc.subject |
Histone-Lysine N-Methyltransferase/genetics |
dc.subject |
Lymphocyte Activation/genetics |
dc.subject |
Neoplasm Proteins/genetics |
dc.subject |
T-Lymphocytes/immunology |
dc.subject |
Signal Transduction |
dc.subject |
Mice, Inbred C57BL |
dc.subject |
Face/abnormalities |
dc.subject |
Gene Expression Regulation |
dc.subject |
Abnormalities, Multiple |
dc.subject |
Mice, Knockout |
dc.subject |
Animals |
dc.subject |
DNA-Binding Proteins/genetics |
dc.subject |
Vestibular Diseases/genetics |
dc.subject |
Myeloid-Lymphoid Leukemia Protein |
dc.subject |
Mice |
dc.subject |
Immunology and Allergy |
dc.subject |
Immunology |
dc.title |
KMT2D regulates activation, localization, and integrin expression by T-cells |
dc.type |
/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article |
dc.description.version |
Peer reviewed |
dc.identifier.doi |
10.3389/fimmu.2024.1341745 |
dc.relation.url |
http://www.scopus.com/inward/record.url?scp=85193471794&partnerID=8YFLogxK |
dc.contributor.department |
Faculty of Earth Sciences |
dc.contributor.department |
Faculty of Medicine |
dc.contributor.department |
Other departments |