Related Experiment Video

Updated: Aug 14, 2026

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
12:59

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes

Published on: September 27, 2013

Inhibitory function of two NFAT family members in lymphoid homeostasis and Th2 development

A M Ranger1, M Oukka, J Rengarajan

  • 1Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115-6017, USA.

Immunity
|December 10, 1998
PubMed

Insights

Nuclear factor of activated T cells (NFAT) regulates T cell signaling. Mice lacking NFATp and NFAT4 exhibit lymphoproliferation and allergic inflammation due to disrupted NFAT balance and Th2 cytokine skewing.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Nuclear factor of activated T cells (NFAT) are transcription factors crucial for T cell receptor (TCR) signaling.
  • NFAT proteins regulate early gene expression following TCR stimulation.

Purpose of the Study:

  • To investigate the role of NFAT family members in T cell homeostasis and immune responses.
  • To determine the consequences of combined NFATp and NFAT4 deficiency in vivo.

Main Methods:

  • Generation and analysis of mice lacking both NFATp and NFAT4.
  • Assessment of lymphocyte populations, TCR signaling thresholds, apoptosis, and cytokine profiles.
  • Evaluation of allergic inflammatory conditions and serum immunoglobulin levels.

Main Results:

  • Mice lacking NFATp and NFAT4 developed a severe lymphoproliferative disorder.
  • These mice showed a lowered TCR signaling threshold and increased resistance to apoptosis due to impaired FasL expression.
  • NFAT-deficient mice exhibited allergic blepharitis, interstitial pneumonitis, and significantly elevated serum IgG1 and IgE levels.
  • A selective increase in Th2 cytokines, potentially due to unopposed NFATc binding to the IL-4 promoter, was observed.

Conclusions:

  • A critical balance among NFAT family members is essential for maintaining lymphoid homeostasis.
  • Disruption of this balance leads to aberrant Th2 activation and severe immune dysregulation.
  • NFAT proteins play a vital role in controlling T cell activation thresholds and apoptosis.

More Related Videos

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets07:12

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets

Published on: April 16, 2015

Isolation of Group 2 Innate Lymphoid Cells from Mouse Nasal Mucosa to Detect the Expression of CD22608:30

Isolation of Group 2 Innate Lymphoid Cells from Mouse Nasal Mucosa to Detect the Expression of CD226

Published on: May 10, 2022

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

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 heterodimer of NF-κB...
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...
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

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 heterodimer of NF-κB...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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.
Naive T cells that have not yet encountered an antigen express two primary CD...
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...