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Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

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...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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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TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

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 are of three kinds RI, RII, and RIII. The RI...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
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Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
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Master Transcription Regulators

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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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
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Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity.

Hiroyuki Hosokawa1, Tomoaki Tanaka, Yutaka Suzuki

  • 1Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.

Proceedings of the National Academy of Sciences of the United States of America
|March 9, 2013
PubMed
Summary

Chromodomain helicase DNA-binding protein 4 (Chd4) works with GATA binding protein 3 (Gata3) to control T helper 2 cell differentiation. This Gata3/Chd4 complex activates Th2 genes while repressing other T cell lineages, crucial for immune responses.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • GATA binding protein 3 (Gata3) is a key transcription factor for T helper 2 (Th2) cell differentiation.
  • The mechanisms by which Gata3 activates Th2-specific genes while repressing other T helper cell lineages remain unclear.

Purpose of the Study:

  • To investigate how Gata3 orchestrates the simultaneous activation of Th2 genes and repression of other Th lineages.
  • To identify the molecular partners of Gata3 involved in regulating Th2 cell differentiation and function.

Main Methods:

  • Co-immunoprecipitation to identify protein complexes involving Gata3.
  • Chromatin immunoprecipitation sequencing (ChIP-seq) to map Gata3 and Chd4 binding sites.
  • Quantitative PCR and cytokine assays to measure gene expression.
  • In vivo mouse model of asthmatic inflammation.

Main Results:

  • Chromodomain helicase DNA-binding protein 4 (Chd4) forms a complex with Gata3 in Th2 cells.
  • The Gata3/Chd4 complex activates Th2 cytokine transcription and represses the Th1 cytokine IFN-γ.
  • Distinct Gata3/Chd4 complexes were identified: a transcriptional activation complex with p300 at Th2 cytokine loci and a repression complex at the Tbx21 locus.
  • Chd4 plays a physiological role in Th2-dependent asthmatic inflammation.

Conclusions:

  • Gata3/Chd4 complexes mediate both gene activation and repression, essential for Th2 cell differentiation.
  • This dual function of Gata3/Chd4 is critical for establishing the Th2 cell lineage and regulating inflammatory responses.
  • Chd4 is a key regulator in Th2-mediated inflammation, highlighting its importance in allergic diseases.