Dissertation/Thesis Abstract

Helios regulates interleukin-2 expression and suppressive function in natural regulatory T cells
by Baine, Ian, Ph.D., Yeshiva University, 2012, 157; 3536054
Abstract (Summary)

The critical role of regulatory T cells in maintaining immune tolerance and preventing autoimmune disease has been well established. Treg cells express the transcription factor Foxp3, which acts as a master regulator of their differentiation and controls their capacity to suppress T cell responses. Treg cells have an intrinsically anergic phenotype and do not produce IL-2 or proliferate upon stimulation ex vivo. Recent reports have identified that Helios, a member of the Ikaros family of transcription factors, is expressed in Treg cells. However, its specific function(s) are not yet fully understood. In this study, we show that Helios regulates IL-2 production in Treg cells by suppressing //2 transcription. Loss of Helios in Treg cells breaks their anergic phenotype and results in de-repression of the //2 locus, allowing Treg cells to display increased baseline proliferation, and to produce IL-2 following stimulation. Conversely, forced expression of Helios in CD4 +Foxp3- Th1 cells results in a loss of their normal ability to produce IL-2. Helios acts by directly binding the //2 promoter and inducing histone deacetylation. We also show that loss of Helios in Treg cells results in decreased Foxp3 binding to the //2 promoter, indicating that Helios is a necessary permissive factor for Foxp3 binding to the //2 promoter. Interestingly, the loss of Helios in Treg cells also causes a decrease in the suppressive capacity of Treg cells. Our results identify Helios as a key regulator of IL-2 expression in Treg cells, contributing to the maintenance of their anergic phenotype.

Indexing (document details)
Advisor: Macian-Juan, Fernando
Commitee: Birshtein, Barbara, Feske, Stefan, Locker, Joseph, Prystowsky, Michael, Zang, Xingxing
School: Yeshiva University
Department: Pathology
School Location: United States -- New York
Source: DAI-B 74/06(E), Dissertation Abstracts International
Subjects: Molecular biology, Genetics, Immunology
Keywords: IL-2, Immune tolerance, T regulatory cells
Publication Number: 3536054
ISBN: 978-1-267-91109-4
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