Loss of TET2 and TET3 in regulatory T cells unleashes effector function

TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine and other oxidized methylcytosines in DNA. Here we examine the role of TET proteins in regulatory T (Treg) cells. Tet2/3(fl/fl)Foxp3(Cre) mice lacking Tet2 and Tet3 in Treg cells develop inflammatory disease, and Treg cells from these m...

Descripción completa

Detalles Bibliográficos
Autores principales: Yue, Xiaojing, Lio, Chan-Wang J., Samaniego-Castruita, Daniela, Li, Xiang, Rao, Anjana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494907/
https://www.ncbi.nlm.nih.gov/pubmed/31043609
http://dx.doi.org/10.1038/s41467-019-09541-y
_version_ 1783415298561409024
author Yue, Xiaojing
Lio, Chan-Wang J.
Samaniego-Castruita, Daniela
Li, Xiang
Rao, Anjana
author_facet Yue, Xiaojing
Lio, Chan-Wang J.
Samaniego-Castruita, Daniela
Li, Xiang
Rao, Anjana
author_sort Yue, Xiaojing
collection PubMed
description TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine and other oxidized methylcytosines in DNA. Here we examine the role of TET proteins in regulatory T (Treg) cells. Tet2/3(fl/fl)Foxp3(Cre) mice lacking Tet2 and Tet3 in Treg cells develop inflammatory disease, and Treg cells from these mice show altered expression of Treg signature genes and upregulation of genes involved in cell cycle, DNA damage and cancer. In littermate mice with severe inflammation, both CD4(+)Foxp3(+) and CD4(+)Foxp3(−) cells show strong skewing towards Tfh/Th17 phenotypes. Wild-type Treg cells in mixed bone marrow chimeras and in Tet2/3(fl/fl)Foxp3(WT/Cre) heterozygous female mice are unable to rescue the aberrant properties of Tet2/3(fl/fl)Foxp3(Cre) Treg cells. Treg cells from Tet2/3(fl/fl)Foxp3(Cre) mice tend to lose Foxp3 expression, and transfer of total CD4(+) T cells isolated from Tet2/3(fl/fl)Foxp3(Cre) mice could elicit inflammatory disease in fully immunocompetent mice. Together, these data indicate that Tet2 and Tet3 are guardians of Treg cell stability and immune homeostasis.
format Online
Article
Text
id pubmed-6494907
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-64949072019-05-03 Loss of TET2 and TET3 in regulatory T cells unleashes effector function Yue, Xiaojing Lio, Chan-Wang J. Samaniego-Castruita, Daniela Li, Xiang Rao, Anjana Nat Commun Article TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine and other oxidized methylcytosines in DNA. Here we examine the role of TET proteins in regulatory T (Treg) cells. Tet2/3(fl/fl)Foxp3(Cre) mice lacking Tet2 and Tet3 in Treg cells develop inflammatory disease, and Treg cells from these mice show altered expression of Treg signature genes and upregulation of genes involved in cell cycle, DNA damage and cancer. In littermate mice with severe inflammation, both CD4(+)Foxp3(+) and CD4(+)Foxp3(−) cells show strong skewing towards Tfh/Th17 phenotypes. Wild-type Treg cells in mixed bone marrow chimeras and in Tet2/3(fl/fl)Foxp3(WT/Cre) heterozygous female mice are unable to rescue the aberrant properties of Tet2/3(fl/fl)Foxp3(Cre) Treg cells. Treg cells from Tet2/3(fl/fl)Foxp3(Cre) mice tend to lose Foxp3 expression, and transfer of total CD4(+) T cells isolated from Tet2/3(fl/fl)Foxp3(Cre) mice could elicit inflammatory disease in fully immunocompetent mice. Together, these data indicate that Tet2 and Tet3 are guardians of Treg cell stability and immune homeostasis. Nature Publishing Group UK 2019-05-01 /pmc/articles/PMC6494907/ /pubmed/31043609 http://dx.doi.org/10.1038/s41467-019-09541-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yue, Xiaojing
Lio, Chan-Wang J.
Samaniego-Castruita, Daniela
Li, Xiang
Rao, Anjana
Loss of TET2 and TET3 in regulatory T cells unleashes effector function
title Loss of TET2 and TET3 in regulatory T cells unleashes effector function
title_full Loss of TET2 and TET3 in regulatory T cells unleashes effector function
title_fullStr Loss of TET2 and TET3 in regulatory T cells unleashes effector function
title_full_unstemmed Loss of TET2 and TET3 in regulatory T cells unleashes effector function
title_short Loss of TET2 and TET3 in regulatory T cells unleashes effector function
title_sort loss of tet2 and tet3 in regulatory t cells unleashes effector function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494907/
https://www.ncbi.nlm.nih.gov/pubmed/31043609
http://dx.doi.org/10.1038/s41467-019-09541-y
work_keys_str_mv AT yuexiaojing lossoftet2andtet3inregulatorytcellsunleasheseffectorfunction
AT liochanwangj lossoftet2andtet3inregulatorytcellsunleasheseffectorfunction
AT samaniegocastruitadaniela lossoftet2andtet3inregulatorytcellsunleasheseffectorfunction
AT lixiang lossoftet2andtet3inregulatorytcellsunleasheseffectorfunction
AT raoanjana lossoftet2andtet3inregulatorytcellsunleasheseffectorfunction

Ejemplares similares