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

Calcium controlled NFATc1 activation enhances suppressive capacity of regulatory T cells isolated from generalized

Prashant S Giri1, Ankit H Bharti2, Rasheedunnisa Begum3

  • 1C. G. Bhakta Institute of Biotechnology, Faculty of Science, Uka Tarsadia University, Surat, Gujarat, India.

Immunology
|June 27, 2022
PubMed

Insights

Generalized vitiligo (GV) involves impaired regulatory T-cells (Tregs) due to reduced calcium levels and NFATc1 signaling. Restoring calcium levels in Tregs can enhance their suppressive capacity, offering potential therapeutic strategies for GV.

Area of Science:

  • Immunology
  • Dermatology
  • Cellular Signaling

Background:

  • Regulatory T-cells (Tregs) play a crucial role in immune homeostasis.
  • Impaired Treg function is implicated in autoimmune and inflammatory conditions like generalized vitiligo (GV).
  • NFAT (nuclear factor of activated T-cells) signaling is critical for T-cell activation and function.

Purpose of the Study:

  • To investigate the role of calcium-mediated NFATc1 signaling in Treg dysfunction in GV.
  • To assess the impact of altered calcium homeostasis on Treg suppressive capacity in GV patients.
  • To explore the potential of calcium restoration as a therapeutic approach for GV.

Main Methods:

  • Quantification of intracellular and plasma calcium levels, calcineurin, NFATc1, and GSK-3β activity in Tregs from GV patients and controls.
  • Assessment of gene and protein expression of key molecules involved in calcium signaling and T-cell function (e.g., ORAI1, IFN-γ, IL-10, TGF-β).
  • Evaluation of Treg suppressive capacity and T-cell proliferation following calcium treatment in vitro.

Main Results:

  • GV patients exhibited reduced plasma and intracellular Treg calcium levels, decreased calcineurin and NFATc1 activity, and altered expression of calcium channel transcripts (ORAI1, CNB, CAM).
  • Elevated GSK-3β activity and GSK3B and DYRK1A transcripts were observed in GV Tregs, correlating with reduced NFATc1 activity.
  • Calcium treatment restored intracellular calcium levels and ORAI1 transcripts in GV Tregs, enhancing calcineurin and NFATc1 activity and improving Treg-mediated suppression of T-cells, while modulating cytokine profiles (increased IL-10, TGF-β; decreased IFN-γ).

Conclusions:

  • Reduced calcium levels and impaired ORAI1-mediated calcium uptake contribute to defective calcineurin-NFATc1 activation and reduced Treg suppressive capacity in GV.
  • Elevated GSK-3β activity is associated with diminished NFATc1 signaling in GV Tregs.
  • The calcium-NFATc1 signaling pathway is a potential therapeutic target for restoring Treg function in GV.
Keywords:
DYRK1AFOXP3GSK-3βNFATc1ORAI1calcineurincalciumcalmodulinimmune suppressionregulatory T-cells (Tregs)

More Related Videos

Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice07:17

Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice

Published on: June 22, 2016

9.9K
Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation15:33

Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation

Published on: August 13, 2013

16.0K

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...
1.4K
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...
7.8K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.5K
Role of Skin in Vitamin D Synthesis01:23

Role of Skin in Vitamin D Synthesis

The skin plays a crucial role in the synthesis of vitamin D, a vital nutrient for various physiological processes in the body. Vitamin D is unique because it can be synthesized in the skin through a series of chemical reactions triggered by exposure to ultraviolet B (UVB) radiation from sunlight.
The solar UV B rays (290-315 nm) are absorbed by the skin, and 7-dehydrocholesterol (provitamin D3) photolyzes it to previtamin D3, which undergoes a rapid transformation to vitamin...
5.6K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.1K
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...
7.6K