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000119264 1001_ $$aTsagaratou, Ageliki$$b0
000119264 245__ $$aTET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells.
000119264 260__ $$aNew York, NY$$bNature America Inc.$$c2017
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000119264 520__ $$aTET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4(+)CD8(+) double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO iNKT cells into immunocompetent recipient mice resulted in an uncontrolled expansion that was dependent on the nonclassical major histocompatibility complex (MHC) protein CD1d, which presents lipid antigens to iNKT cells. Our data indicate that TET proteins regulate iNKT cell fate by ensuring their proper development and maturation and by suppressing aberrant proliferation mediated by the T cell antigen receptor (TCR).
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000119264 7001_ $$aGonzález-Avalos, Edahí$$b1
000119264 7001_ $$aRautio, Sini$$b2
000119264 7001_ $$aScott-Browne, James P$$b3
000119264 7001_ $$aTogher, Susan$$b4
000119264 7001_ $$aPastor, William A$$b5
000119264 7001_ $$0http://orcid.org/0000-0002-3901-347X$$aRothenberg, Ellen V$$b6
000119264 7001_ $$0P:(DE-HGF)0$$aChavez, Lukas$$b7
000119264 7001_ $$aLähdesmäki, Harri$$b8
000119264 7001_ $$aRao, Anjana$$b9
000119264 773__ $$0PERI:(DE-600)2026412-4$$a10.1038/ni.3630$$gVol. 18, no. 1, p. 45 - 53$$n1$$p45 - 53$$tNature immunology$$v18$$x1529-2916$$y2017
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