Demethylation analysis of the FOXP3 locus shows quantitative defects of regulatory T cells in IPEX-like syndrome.

Détails

ID Serval
serval:BIB_3A2537950A25
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Demethylation analysis of the FOXP3 locus shows quantitative defects of regulatory T cells in IPEX-like syndrome.
Périodique
Journal of Autoimmunity
Auteur⸱e⸱s
Barzaghi F., Passerini L., Gambineri E., Ciullini Mannurita S., Cornu T., Kang E.S., Choe Y.H., Cancrini C., Corrente S., Ciccocioppo R., Cecconi M., Zuin G., Discepolo V., Sartirana C., Schmidtko J., Ikinciogullari A., Ambrosi A., Roncarolo M.G., Olek S., Bacchetta R.
ISSN
1095-9157 (Electronic)
ISSN-L
0896-8411
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
38
Numéro
1
Pages
49-58
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Résumé
Immune dysregulation, Polyendocrinopathy, Enteropathy X-linked (IPEX) syndrome is a unique example of primary immunodeficiency characterized by autoimmune manifestations due to defective regulatory T (Treg) cells, in the presence of FOXP3 mutations. However, autoimmune symptoms phenotypically resembling IPEX often occur in the absence of detectable FOXP3 mutations. The cause of this "IPEX-like" syndrome presently remains unclear. To investigate whether a defect in Treg cells sustains the immunological dysregulation in IPEX-like patients, we measured the amount of peripheral Treg cells within the CD3(+) T cells by analysing demethylation of the Treg cell-Specific-Demethylated-Region (TSDR) in the FOXP3 locus and demethylation of the T cell-Specific-Demethylated-Region (TLSDR) in the CD3 locus, highly specific markers for stable Treg cells and overall T cells, respectively. TSDR demethylation analysis, alone or normalized for the total T cells, showed that the amount of peripheral Treg cells in a cohort of IPEX-like patients was significantly reduced, as compared to both healthy subjects and unrelated disease controls. This reduction could not be displayed by flow cytometric analysis, showing highly variable percentages of FOXP3(+) and CD25(+)FOXP3(+) T cells. These data provide evidence that a quantitative defect of Treg cells could be considered a common biological hallmark of IPEX-like syndrome. Since Treg cell suppressive function was not impaired, we propose that this reduction per se could sustain autoimmunity.
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/04/2012 14:10
Dernière modification de la notice
20/08/2019 13:29
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