Related Experiment Video

Updated: Jun 10, 2026

Imaging Initial Ca2+ Microdomains in Primary T Cells
05:56

Imaging Initial Ca2+ Microdomains in Primary T Cells

Published on: October 4, 2024

The nonphagocytic NADPH oxidase Duox1 mediates a positive feedback loop during T cell receptor signaling

Jaeyul Kwon1, Kristen E Shatynski, Haiyan Chen

  • 1Center for Vascular and Inflammatory Diseases, Department of Microbiology and Immunology, University of Maryland School of Medicine, 800 West Baltimore Street, Baltimore, MD 21201, USA. kwonja@niaid.nih.gov

Science Signaling
|August 5, 2010
PubMed

Insights

The enzyme Duox1 generates hydrogen peroxide (H2O2) to boost T cell receptor (TCR) signaling. This reactive oxygen species production is crucial for T cell activation and cytokine release, highlighting Duox1

Area of Science:

  • Immunology
  • Cell Signaling
  • Biochemistry

Background:

  • Reactive oxygen species (ROS) production, often by NADPH oxidases, is integral to cellular receptor-mediated signaling.
  • The nonphagocytic, calcium-dependent NADPH oxidase Duox1's role in T cells remains largely uncharacterized.

Purpose of the Study:

  • To elucidate the function of Duox1 in primary human CD4(+) T cells and T cell lines.
  • To investigate Duox1's involvement in T cell receptor (TCR) signaling pathways.

Main Methods:

  • Investigated Duox1 binding to inositol 1,4,5-trisphosphate receptor 1.
  • Utilized transient and stable knockdown of Duox1 to assess its impact on TCR signaling.
  • Analyzed the phosphorylation of ZAP-70, calcium ion influx, and extracellular signal-regulated kinase activation.

Main Results:

  • Duox1 is essential for early TCR-stimulated hydrogen peroxide (H2O2) production via TCR-proximal kinases.
  • Duox1 knockdown impaired TCR signaling, including ZAP-70 phosphorylation, Ca(2+) influx, and ERK activation.
  • Duox1 inactivation of SHP2 phosphatase promoted ZAP-70 phosphorylation and its association with Lck and CD3zeta.

Conclusions:

  • Duox1 activation, downstream of TCR signals, generates H2O2 that positively feeds back to enhance TCR signaling.
  • Duox1 plays a critical role in sustaining T cell activation and cytokine production.
  • Duox1 represents a key regulator of T cell immune responses.

More Related Videos

In vivo Imaging Method to Distinguish Acute and Chronic Inflammation07:10

In vivo Imaging Method to Distinguish Acute and Chronic Inflammation

Published on: August 16, 2013

Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models10:42

Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models

Published on: October 22, 2012

Related Concept Videos

Cell Signaling Feedback Loops01:07

Cell Signaling Feedback Loops

Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
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...
Positive and Negative Feedback Loops01:18

Positive and Negative Feedback Loops

Animal organs and organ systems constantly adjust to internal and external changes through a process called homeostasis ("steady state"). Examples of these changes include regulation of the level of glucose or calcium in the blood or internal responses to external temperatures. Homeostasis requires  maintaining an internal dynamic equilibrium:
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...
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.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...