Molecular Markers Distinguishing T Cell Subtypes With TSDR Strand-Bias Methylation

Human regulatory CD4+CD25+FOXP3+ T cells (Treg) play important roles in the maintenance of self-tolerance and immune homeostasis in various disease settings and are also involved in the suppression of effective immune responses. These cells are heterogeneous in phenotype and function, and the abilit...

Full description

Bibliographic Details
Main Authors: Ekaterina Minskaia, Barbara C. Saraiva, Maria M. V. Soares, Rita I. Azevedo, Ruy M. Ribeiro, Saumya D. Kumar, Ana I. S. Vieira, João F. Lacerda
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-11-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2018.02540/full
_version_ 1818850310154616832
author Ekaterina Minskaia
Barbara C. Saraiva
Maria M. V. Soares
Rita I. Azevedo
Ruy M. Ribeiro
Saumya D. Kumar
Ana I. S. Vieira
João F. Lacerda
author_facet Ekaterina Minskaia
Barbara C. Saraiva
Maria M. V. Soares
Rita I. Azevedo
Ruy M. Ribeiro
Saumya D. Kumar
Ana I. S. Vieira
João F. Lacerda
author_sort Ekaterina Minskaia
collection DOAJ
description Human regulatory CD4+CD25+FOXP3+ T cells (Treg) play important roles in the maintenance of self-tolerance and immune homeostasis in various disease settings and are also involved in the suppression of effective immune responses. These cells are heterogeneous in phenotype and function, and the ability to reliably distinguish between various FOXP3-expressing subpopulations can affect the development of successful therapies. This study demonstrates that hypomethylated CpG sites, present in four regions of the FOXP3 locus, CAMTA1 and FUT7 gene regions, can be used to distinguish several subsets of Treg from conventional CD4+ T lymphocytes (Tcon) in donors of both genders. We describe a previously unreported strand-bias hemimethylation pattern in FOXP3 promoter and TSDR in donors of both genders, with the coding strand being demethylated within promoter and methylated within TSDR in all CD4+ lymphocyte subtypes, whereas the template strand follows the previously described pattern of methylation with both regions being more demethylated in Treg subtypes and mostly methylated in Tcon. This strand-specific approach within the TSDR may prove to be instrumental in correctly defining Treg subsets in health and in disease.
first_indexed 2024-12-19T06:47:06Z
format Article
id doaj.art-65120597b8e849f18e1de320b89b77ee
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-12-19T06:47:06Z
publishDate 2018-11-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj.art-65120597b8e849f18e1de320b89b77ee2022-12-21T20:31:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02540396019Molecular Markers Distinguishing T Cell Subtypes With TSDR Strand-Bias MethylationEkaterina Minskaia0Barbara C. Saraiva1Maria M. V. Soares2Rita I. Azevedo3Ruy M. Ribeiro4Saumya D. Kumar5Ana I. S. Vieira6João F. Lacerda7Faculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular–João Lobo Antunes, Lisbon, PortugalFaculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular–João Lobo Antunes, Lisbon, PortugalFaculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular–João Lobo Antunes, Lisbon, PortugalFaculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular–João Lobo Antunes, Lisbon, PortugalDepartmento de Biomatemática, Faculdade de Medicina da Universidade de Lisboa, Lisbon, PortugalFaculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular–João Lobo Antunes, Lisbon, PortugalFaculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular–João Lobo Antunes, Lisbon, PortugalFaculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular–João Lobo Antunes, Lisbon, PortugalHuman regulatory CD4+CD25+FOXP3+ T cells (Treg) play important roles in the maintenance of self-tolerance and immune homeostasis in various disease settings and are also involved in the suppression of effective immune responses. These cells are heterogeneous in phenotype and function, and the ability to reliably distinguish between various FOXP3-expressing subpopulations can affect the development of successful therapies. This study demonstrates that hypomethylated CpG sites, present in four regions of the FOXP3 locus, CAMTA1 and FUT7 gene regions, can be used to distinguish several subsets of Treg from conventional CD4+ T lymphocytes (Tcon) in donors of both genders. We describe a previously unreported strand-bias hemimethylation pattern in FOXP3 promoter and TSDR in donors of both genders, with the coding strand being demethylated within promoter and methylated within TSDR in all CD4+ lymphocyte subtypes, whereas the template strand follows the previously described pattern of methylation with both regions being more demethylated in Treg subtypes and mostly methylated in Tcon. This strand-specific approach within the TSDR may prove to be instrumental in correctly defining Treg subsets in health and in disease.https://www.frontiersin.org/article/10.3389/fimmu.2018.02540/fullFOXP3CAMTAFUT7regulatory T lymphocytesepigeneticsstrand-bias methylation
spellingShingle Ekaterina Minskaia
Barbara C. Saraiva
Maria M. V. Soares
Rita I. Azevedo
Ruy M. Ribeiro
Saumya D. Kumar
Ana I. S. Vieira
João F. Lacerda
Molecular Markers Distinguishing T Cell Subtypes With TSDR Strand-Bias Methylation
Frontiers in Immunology
FOXP3
CAMTA
FUT7
regulatory T lymphocytes
epigenetics
strand-bias methylation
title Molecular Markers Distinguishing T Cell Subtypes With TSDR Strand-Bias Methylation
title_full Molecular Markers Distinguishing T Cell Subtypes With TSDR Strand-Bias Methylation
title_fullStr Molecular Markers Distinguishing T Cell Subtypes With TSDR Strand-Bias Methylation
title_full_unstemmed Molecular Markers Distinguishing T Cell Subtypes With TSDR Strand-Bias Methylation
title_short Molecular Markers Distinguishing T Cell Subtypes With TSDR Strand-Bias Methylation
title_sort molecular markers distinguishing t cell subtypes with tsdr strand bias methylation
topic FOXP3
CAMTA
FUT7
regulatory T lymphocytes
epigenetics
strand-bias methylation
url https://www.frontiersin.org/article/10.3389/fimmu.2018.02540/full
work_keys_str_mv AT ekaterinaminskaia molecularmarkersdistinguishingtcellsubtypeswithtsdrstrandbiasmethylation
AT barbaracsaraiva molecularmarkersdistinguishingtcellsubtypeswithtsdrstrandbiasmethylation
AT mariamvsoares molecularmarkersdistinguishingtcellsubtypeswithtsdrstrandbiasmethylation
AT ritaiazevedo molecularmarkersdistinguishingtcellsubtypeswithtsdrstrandbiasmethylation
AT ruymribeiro molecularmarkersdistinguishingtcellsubtypeswithtsdrstrandbiasmethylation
AT saumyadkumar molecularmarkersdistinguishingtcellsubtypeswithtsdrstrandbiasmethylation
AT anaisvieira molecularmarkersdistinguishingtcellsubtypeswithtsdrstrandbiasmethylation
AT joaoflacerda molecularmarkersdistinguishingtcellsubtypeswithtsdrstrandbiasmethylation