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Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

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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.
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General Transcription Factors01:30

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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...
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Combinatorial Gene Control02:33

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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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T Cell Activation and Clonal Selection01:22

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Master Transcription Regulators02:23

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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...
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Inflammatory Response01:28

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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.
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Updated: Sep 11, 2025

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Na&#239;ve CD4+ T Cells Using a TGF-&#946;-containing Protocol
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Normal Treg homeostasis and suppressive function require both FOXP1 and FOXP4.

Dachuan Dong1,2,3, Vishal J Sindhava4, Ananthakrishnan Ganesan3

  • 1Geriatric Research Education and Clinical Center, Veterans Administration Palo Alto Health Care System, Palo Alto, California, USA.

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|August 12, 2025
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Summary

FOXP1 and FOXP4 proteins are crucial for regulatory T cell (Treg) function. Their combined absence in Tregs leads to immune dysfunction, autoimmunity, and early death in mice.

Keywords:
Adaptive immunityAutoimmunityImmunologyTregs

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • FOXP3+ regulatory T cells (Tregs) are essential for maintaining immune tolerance.
  • FOXP1 is known to influence Treg function, but FOXP4's role is largely uncharacterized.
  • Understanding FOXP family interactions in Tregs is critical for immune regulation.

Purpose of the Study:

  • To investigate the functional interactions between FOXP1 and FOXP4 in mouse Treg cells.
  • To determine the consequences of combined FOXP1 and FOXP4 deficiency in Tregs.

Main Methods:

  • Generation of mouse models with specific genetic deletion of Foxp1, Foxp4, or both in Treg cells.
  • Analysis of Treg cell phenotype, suppressive function, and immune responses.
  • Investigation of FOXP1 and FOXP4 binding to the Il2ra promoter.

Main Results:

  • Combined deficiency of FOXP1 and FOXP4 in Tregs caused lymphoproliferation, inflammation, autoimmunity, and early lethality.
  • Absence of both proteins led to an activated Treg phenotype, impaired suppressive function, enhanced germinal center response, and increased proinflammatory cytokine production.
  • FOXP1 and FOXP4 were found to regulate CD25 expression by binding to Il2ra promoter regions.

Conclusions:

  • FOXP1 and FOXP4 play non-redundant but cooperative roles in Treg cell function.
  • FOXP4 has an insufficient role alone, highlighting the importance of FOXP1 in Treg-mediated immune tolerance.
  • Combined FOXP1/FOXP4 deficiency severely disrupts Treg function, leading to autoimmune disease.