Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

1.4K
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...
1.4K
Master Transcription Regulators02:23

Master Transcription Regulators

7.0K
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...
7.0K
Abnormal Proliferation02:23

Abnormal Proliferation

4.6K
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...
4.6K
General Transcription Factors01:30

General Transcription Factors

5.5K
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...
5.5K
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

993
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
993
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

3.1K
3.1K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Newborn screening reduces survival disparities in SCID after stem cell transplant: A PIDTC report.

Journal of human immunity·2026
Same author

Retraction Note: Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance.

Nature communications·2026
Same author

An early protective effect of IL-9 in murine systemic lupus erythematosus.

ImmunoHorizons·2026
Same author

cGAS bends unpaired DNA to form an unconventional structure that hyperactivates the innate immune response.

bioRxiv : the preprint server for biology·2026
Same author

Local oxygen tension dictates hematopoietic cell growth and potency.

Leukemia·2026
Same author

X-linked SEPTIN6-related congenital neutropenia and B cell deficiency.

Journal of human immunity·2026

Related Experiment Video

Updated: Sep 6, 2025

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
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

20.7K

FOXP3 exon 2 controls Treg stability and autoimmunity.

Jianguang Du1, Qun Wang1, Shuangshuang Yang1,2

  • 1Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Science Immunology
|June 24, 2022
PubMed
Summary

The human FOXP3 gene produces two isoforms. The shorter FOXP3 ΔE2 isoform, lacking exon 2, causes IPEX syndrome and autoimmune disease by destabilizing regulatory T cells.

More Related Videos

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
14:23

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells

Published on: April 16, 2012

24.3K
Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation
15:33

Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation

Published on: August 13, 2013

16.0K

Related Experiment Videos

Last Updated: Sep 6, 2025

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
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

20.7K
Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
14:23

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells

Published on: April 16, 2012

24.3K
Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation
15:33

Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation

Published on: August 13, 2013

16.0K

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Human FOXP3 gene produces two major isoforms via alternative splicing: FOXP3 FL and FOXP3 ΔE2.
  • The functional differences between these FOXP3 isoforms in regulatory T cell (Treg) function remain largely unknown.

Purpose of the Study:

  • To investigate the distinct roles of FOXP3 FL and FOXP3 ΔE2 isoforms in maintaining immune homeostasis.
  • To elucidate the mechanisms by which FOXP3 exon 2 influences Treg stability and function.

Main Methods:

  • Analysis of patients with FOXP3 isoform-specific expression.
  • Generation and analysis of mouse models with Foxp3 exon 2 deletion.
  • In vitro functional assays of regulatory T cells expressing different FOXP3 isoforms.
  • Transcriptional profiling to identify downstream targets of FOXP3 isoforms.

Main Results:

  • Patients expressing only FOXP3 ΔE2 develop IPEX syndrome, indicating a failure in self-tolerance.
  • Foxp3 exon 2-deficient mice exhibit exaggerated T follicular helper (Tfh) and B cell responses, leading to autoimmunity.
  • FOXP3 ΔE2-expressing Tregs are unstable in vivo, inducing autoimmunity despite normal in vitro suppressive function.
  • FOXP3 ΔE2 alters the expression of specific cytokines and Treg-associated genes without affecting DNA binding.

Conclusions:

  • The FOXP3 exon 2 region is critical for maintaining Treg stability and immune homeostasis.
  • Deficiency in FOXP3 exon 2 leads to Treg instability and the development of severe autoimmune diseases.
  • FOXP3 isoforms play distinct roles in regulating immune responses and preventing autoimmunity.