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• W4303474747 abstract "Abstract Objective There is a clinical need to understand how dysregulated thymocyte development, caused by pathogenic variants in the gene encoding the histone-modifying enzyme, lysine methyltransferase 2D ( KMT2D ), contributes to immune dysfunction, including immune deficiency, autoimmunity, and lymphoproliferative sequela, and immune-driven mortality in individuals with Kabuki syndrome type 1 (KS1). Methods We studied peripheral T cells and thymocytes in both individuals with KS1 and murine constitutive and conditional targeted Kmt2d in T cells and hematopoietic lineages. KMT2D target genes, identified by RNA-sequencing of murine Kmt2d -knockout single-positive thymocytes, were validated with H3K4me3 ChIP-PCR and flow cytometry. Results Recent thymic emigrant (RTE) and naïve T cells were reduced, and memory and double-negative (DN)-T cells were expanded in human KS1 and murine models. Kmt2d loss led to Mature 1 CD8 + -single positive (SP) thymocyte accumulation and a decrease in SP thymocyte egress licensing expression (normally associated with the Mature 2 phenotype). Splenomegaly is associated with hematopoietic-driven Kmt2d loss and brings to light potential overlapping phenotypes with lymphoproliferative syndromes. Finally, we identified a KMT2D-regulated cluster of integrins which likely mediates aspects of the T cell egression. Conclusions Single-positive thymocyte populations deficient in Kmt2d display less integrin, less maturation, and less egress licensing gene expression; thereby, altering the downstream peripheral T cell composition that contribute to the observed KS1-associated immune deficiency. T cell intrinsic Kmt2d loss increases the percentage of peripheral DNT cells potentially through dysregulated apoptotic signaling, while hematopoietic-driven Kmt2d loss predisposes to splenomegaly; therefore, loss of Kmt2d recapitulates several distinct features of lymphoproliferative syndromes." @default.
• W4303474747 created "2022-10-08" @default.
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• W4303474747 date "2022-10-07" @default.
• W4303474747 modified "2023-09-24" @default.
• W4303474747 title "KMT2D Regulates thymic Egress by Modulating Maturation and integrin Expression" @default.
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• W4303474747 cites W1945715178 @default.
• W4303474747 cites W1976505472 @default.
• W4303474747 cites W1979155556 @default.
• W4303474747 cites W1989316550 @default.
• W4303474747 cites W1998162118 @default.
• W4303474747 cites W2001311465 @default.
• W4303474747 cites W2001640037 @default.
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• W4303474747 cites W2014677321 @default.
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• W4303474747 cites W2056947996 @default.
• W4303474747 cites W2057781689 @default.
• W4303474747 cites W2061093976 @default.
• W4303474747 cites W2073340956 @default.
• W4303474747 cites W2077059405 @default.
• W4303474747 cites W2079116568 @default.
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• W4303474747 cites W2099890567 @default.
• W4303474747 cites W2114843025 @default.
• W4303474747 cites W2117131162 @default.
• W4303474747 cites W2120500419 @default.
• W4303474747 cites W2124610030 @default.
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• W4303474747 cites W2128016314 @default.
• W4303474747 cites W2128245545 @default.
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• W4303474747 cites W2146494362 @default.
• W4303474747 cites W2146734921 @default.
• W4303474747 cites W2149441684 @default.
• W4303474747 cites W2155048915 @default.
• W4303474747 cites W2156483545 @default.
• W4303474747 cites W2159847432 @default.
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• W4303474747 doi "https://doi.org/10.1101/2022.10.04.510662" @default.
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