Regulation of IL-2 gene expression by Siva and FOXP3 in human T cells

Hench, Virginia K.; Su, Lishan

doi:10.1186/1471-2172-12-54

Cited by 9 publications

(9 citation statements)

References 61 publications

(104 reference statements)

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“…It is not known if SF2/ASF activates transcriptional initiation or elongation in the regulation of IL-2. A number of transcription factors such as NFAT, AP-1, and NF-κB are known to be important in IL-2 transcription control (14,29). We previously showed that increased expression of the cAMP response element modulator α repressor (30) and reduced expression and binding of the AP-1 activator (31) are factors that contribute to the reduced IL-2 expression in T cells from patients with SLE.…”

Section: Discussionmentioning

confidence: 99%

Splicing factor SF2/ASF rescues IL-2 production in T cells from systemic lupus erythematosus patients by activating IL-2 transcription

Moulton

Grammatikos

Fitzgerald

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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T cells from patients with systemic lupus erythematosus (SLE) produce insufficient amounts of the vital cytokine IL-2. We previously showed that SLE T cells express decreased levels of the T-cell receptor-CD3ζ chain and forced expression of CD3ζ into SLE T cells restores IL-2 production. We recently showed that the serine arginine protein splicing factor 2/alternative splicing factor (SF2/ASF) enhances the expression of CD3ζ chain by limiting the production of an unstable splice variant. Here we demonstrate that SF2/ASF levels are decreased in patients with SLE and more so in those with active disease. More importantly, we reveal a function of SF2/ASF, independent of T-cell receptor/CD3 signaling, whereby it is recruited to the IL-2 promoter, increases transcriptional activity, and enhances IL-2 production in SLE T cells. Our results demonstrate that SF2/ASF regulates IL-2 production and that decreased SF2/ASF expression in SLE T cells contributes to deficient IL-2 production.

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Section: Discussionmentioning

confidence: 99%

Splicing factor SF2/ASF rescues IL-2 production in T cells from systemic lupus erythematosus patients by activating IL-2 transcription

Moulton

Grammatikos

Fitzgerald

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…The binding of Foxp3 to RORγt prevents the activation of RORγt-mediated IL-17A transcription, thus inhibiting the polarization of cells toward a Th17 phenotype (125). Hench and co-workers identified another Foxp3 binding partner, Siva; the interaction between Foxp3 and Siva potentiates the repressive effect on NF-κB activity compared to that performed by Foxp3 alone (158). Foxp3induced activation or repression of transcription of specific target genes is also maintained through the induction of epigenetic modifications thanks to the ability of Foxp3 to bind and recruit chromatin remodeling factors.…”

Section: Induction Of Treg Cell-associated Transcriptional Programsmentioning

confidence: 99%

Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation

et al. 2020

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The discovery of the transcription factor Forkhead box-p3 (Foxp3) has shed fundamental insights into the understanding of the molecular determinants leading to generation and maintenance of T regulatory (Treg) cells, a cell population with a key immunoregulatory role. Work over the past few years has shown that fine-tuned transcriptional and epigenetic events are required to ensure stable expression of Foxp3 in Treg cells. The equilibrium between phenotypic plasticity and stability of Treg cells is controlled at the molecular level by networks of transcription factors that bind regulatory sequences, such as enhancers and promoters, to regulate Foxp3 expression. Recent reports have suggested that specific modifications of DNA and histones are required for the establishment of the chromatin structure in conventional CD4 + T (Tconv) cells for their future differentiation into the Treg cell lineage. In this review, we discuss the molecular events that control Foxp3 gene expression and address the associated alterations observed in human diseases. Also, we explore how Foxp3 influences the gene expression programs in Treg cells and how unique properties of Treg cell subsets are defined by other transcription factors.

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“…The formation of either homodimeric or heterodimeric Foxp3 protein complexes occurs when a leucine zipper is used which associates with the IL-2 promoter in vivo. Scientific studies have also shown that the multimerization of the Foxp3 protein is extremely important for the proper functioning of Treg lymphocytes [92][93][94][95].…”

Section: Interactions Of Foxp3 Protein With Proteins and Transcriptio...mentioning

confidence: 99%

The Importance of the Transcription Factor Foxp3 in the Development of Primary Immunodeficiencies

Mertowska

Mertowski

Podgajna

et al. 2022

JCM

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Transcription factors are an extremely important group of proteins that are responsible for the process of selective activation or deactivation of other cellular proteins, usually at the last stage of signal transmission in the cell. An important family of transcription factors that regulate the body’s response is the FOX family which plays an important role in regulating the expression of genes involved in cell growth, proliferation, and differentiation. The members of this family include the intracellular protein Foxp3, which regulates the process of differentiation of the T lymphocyte subpopulation, and more precisely, is responsible for the development of regulatory T lymphocytes. This protein influences several cellular processes both directly and indirectly. In the process of cytokine production regulation, the Foxp3 protein interacts with numerous proteins and transcription factors such as NFAT, nuclear factor kappa B, and Runx1/AML1 and is involved in the process of histone acetylation in condensed chromatin. Malfunctioning of transcription factor Foxp3 caused by the mutagenesis process affects the development of disorders of the immune response and autoimmune diseases. This applies to the impairment or inability of the immune system to fight infections due to a disruption of the mechanisms supporting immune homeostasis which in turn leads to the development of a special group of disorders called primary immunodeficiencies (PID). The aim of this review is to provide information on the role of the Foxp3 protein in the human body and its involvement in the development of two types of primary immunodeficiency diseases: IPEX (Immunodysregulation Polyendocrinopathy Enteropathy X-linked syndrome) and CVID (Common Variable Immunodeficiency).

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Regulation of IL-2 gene expression by Siva and FOXP3 in human T cells

Cited by 9 publications

References 61 publications

Splicing factor SF2/ASF rescues IL-2 production in T cells from systemic lupus erythematosus patients by activating IL-2 transcription

Splicing factor SF2/ASF rescues IL-2 production in T cells from systemic lupus erythematosus patients by activating IL-2 transcription

Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation

The Importance of the Transcription Factor Foxp3 in the Development of Primary Immunodeficiencies

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