Related Experiment Video
Updated: Apr 11, 2026
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
21.9K
Inflammation negatively regulates FOXP3 and regulatory T-cell function via DBC1
Yayi Gao1, Jiayou Tang2, Weiqian Chen3
1Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China; Clinical Immunology Center, Third Affiliated Hospital at Sun Yat-Sen University, Guangzhou, 510630, China;
Summary
Deleted in breast cancer 1 (DBC1) stabilizes the crucial FOXP3 protein in Treg cells. DBC1 deficiency enhances Treg cell function during inflammation, offering a new therapeutic target for autoimmune diseases.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Regulatory T (Treg) cells are essential for immune homeostasis.
- The molecular mechanisms governing FOXP3 complex stability and Treg cell function are not fully understood.
Purpose of the Study:
- To identify novel regulators of FOXP3 stability.
- To investigate the role of Deleted in breast cancer 1 (DBC1) in Treg cell function and inflammatory diseases.
Main Methods:
- Co-immunoprecipitation assays to confirm DBC1-FOXP3 interaction.
- Western blotting to assess FOXP3 degradation.
- Treg cell functional assays in vitro.
- In vivo studies using Dbc1-deficient mice to model experimental autoimmune encephalomyelitis and colitis.
Main Results:
- DBC1 physically interacts with FOXP3, forming a key component of the FOXP3 complex.
- DBC1 depletion significantly reduces FOXP3 degradation under inflammatory conditions.
- Treg cells from Dbc1-deficient mice exhibit enhanced resistance to inflammation-induced dysfunction.
- Dbc1 deficiency ameliorates disease severity and onset in mouse models of autoimmune diseases.
Conclusions:
- DBC1 is a critical regulator of FOXP3 stability, particularly during inflammation.
- The DBC1-FOXP3 interaction provides a novel mechanism for controlling Treg cell function.
- Targeting the DBC1-FOXP3 pathway presents a potential therapeutic strategy for inflammatory and autoimmune disorders.
More Related Videos
Related Concept Videos
01:24T Cell Types and Functions
3.4K
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...
3.4K
02:23Master Transcription Regulators
8.0K
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...
8.0K
01:28Inflammatory Response
19.5K
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
19.5K
02:23Abnormal Proliferation
5.4K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
01:15Receptor Downregulation in MVBs
3.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
3.0K
02:26NF-κB-dependent Signaling Pathway
10.6K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
10.6K