Author(s): Minskaia, Ekaterina ; Saraiva, Bárbara C. ; Soares, Maria Vieira ; Azevedo, Rita I. ; Ribeiro, Ruy M. ; Kumar, Saumya ; Vieira, Ana I. S. ; Lacerda, João
Date: 2018
Persistent ID: http://hdl.handle.net/10451/45068
Origin: Repositório da Universidade de Lisboa
Project/scholarship: info:eu-repo/grantAgreement/FCT/3599-PPCDT/HMSP-ICT%2F0001%2F2011/PT;
Subject(s): Strand-bias methylation; CAMTA; FOXP3; FUT7; Epigenetics; Regulatory T lymphocytes
Copyright © 2018 Minskaia, Saraiva, Soares, Azevedo, Ribeiro, Kumar, Vieira and Lacerda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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.
This research was funded by: Fundação para a Ciência e Tecnologia, Portugal under the Harvard Medical School–Portugal Program project Induction of Immune Tolerance in Human Allogeneic Hematopoietic Stem Cell Transplantation (HMSP-ICT/0001/2011), Gabinete de Apoio à Investigação Científica, Tecnológica e Inovação, GAPIC (Faculdade de Medicina ULisboa, GAPIC-04-2016 Project 20160011), LISBOA-01-0145-FEDER-007391 (project co-funded by FEDER through POR Lisboa 2020—Programa Operacional Regional de Lisboa, PORTUGAL 2020 and Fundação para a Ciência e a Tecnologia) and ENLIGHT-TEN project (European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 675395).
