Related Experiment Video
Updated: Jun 16, 2025
08:20
In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
Published on: December 30, 2016
20.4K
T-regulatory cells require Sin3a for stable expression of Foxp3
Lanette M Christensen1, Tatiana Akimova1,2, Liqing Wang2
1Division of Transplant Immunology, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Frontiers in Immunology
|August 19, 2024
Summary
Sin3a is crucial for T-regulatory (Treg) cell function. Its deletion causes fatal autoimmunity by impairing Treg stability, Foxp3 expression, and suppressive capacity, highlighting Sin3a
Area of Science:
- Immunology
- Molecular Biology
- Epigenetics
Background:
- Histone deacetylases 1 and 2 (HDAC1/2) regulate T-regulatory (Treg) cell transcription.
- Sin3a is a known cofactor for HDAC1/2, but its specific role in Tregs is unknown.
Purpose of the Study:
- To investigate the function of Sin3a in Foxp3+ Tregs.
- To determine the consequences of Sin3a deletion on Treg maintenance and function.
Main Methods:
- Conditional deletion of Sin3a in Foxp3+ Tregs.
- Analysis of Treg numbers, suppressive function, and immune cell activation.
- Assessment of Foxp3 expression, CNS2 CpG demethylation, and protein stability.
Main Results:
- Sin3a deletion led to fatal autoimmunity with reduced Treg numbers and impaired suppressive function.
- Effector T-cell activation, autoantibody production, and tissue injury were observed.
- Sin3a deletion decreased Foxp3 transcription, abolished CNS2 CpG demethylation, and reduced Foxp3 protein stability, increasing ex-Treg populations.
Conclusions:
- Sin3a is essential for maintaining Treg identity and function.
- Sin3a plays a critical role in regulating Foxp3 expression and stability within Tregs.
Related Concept Videos
02:23Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
02:04Co-activators and Co-repressors
7.3K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.3K
01:24T Cell Types and Functions
964
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
964
01:16TGF - β Signaling Pathway
7.3K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K
01:30General Transcription Factors
5.2K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.2K
02:36RNA Polymerase II Accessory Proteins
9.1K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.1K