Related Experiment Video

Updated: Apr 18, 2026

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces
07:55

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces

Published on: January 7, 2020

8.0K

Proinflammatory TLR signalling is regulated by a TRAF2-dependent proteolysis mechanism in macrophages

Jin Jin1, Yichuan Xiao1, Hongbo Hu1

  • 1Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston, Texas 77030, USA.

Nature Communications
|January 8, 2015
PubMed

Insights

TRAF2 acts as an anti-inflammatory molecule by controlling key transcription factors, thus limiting toll-like receptor (TLR) signaling and reducing inflammatory responses in macrophages. Its absence exacerbates inflammatory diseases like colitis and promotes tumor growth.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Toll-like receptor (TLR) signaling is crucial for innate immunity but its dysregulation drives inflammatory disorders.
  • TRAF2 is a key signaling molecule in immune responses.

Purpose of the Study:

  • To investigate the role of TRAF2 in regulating TLR-stimulated inflammatory responses in macrophages.
  • To elucidate the molecular mechanisms by which TRAF2 controls inflammatory signaling.

Main Methods:

  • Myeloid cell-specific ablation of TRAF2 in mice.
  • Analysis of proinflammatory cytokine expression in macrophages.
  • Assessment of colitis severity in an animal model.
  • Investigation of transcription factor (c-Rel, IRF5) accumulation.
  • Studies on proteasome-dependent degradation pathways involving TRAF3 and cIAP.

Main Results:

  • TRAF2 deficiency in myeloid cells significantly enhances TLR-stimulated proinflammatory cytokine production.
  • Absence of TRAF2 leads to accumulation of transcription factors c-Rel and IRF5.
  • TRAF2 regulates c-Rel and IRF5 stability through a proteasome-dependent mechanism involving TRAF3 and cIAP.
  • TRAF2 deficiency exacerbates experimental colitis and promotes tumor growth by affecting tumor-associated macrophages.

Conclusions:

  • TRAF2 possesses an unexpected anti-inflammatory function by limiting TLR signaling.
  • A proteasome-dependent mechanism involving TRAF2, TRAF3, and cIAP controls the stability of c-Rel and IRF5, thereby regulating inflammatory cytokine production.
  • Targeting TRAF2-mediated pathways may offer therapeutic strategies for inflammatory diseases and cancer.

More Related Videos

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling09:51

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling

Published on: July 26, 2017

13.1K
Using RNA-interference to Investigate the Innate Immune Response in Mouse Macrophages12:47

Using RNA-interference to Investigate the Innate Immune Response in Mouse Macrophages

Published on: November 3, 2014

12.3K

Related Concept Videos

Inflammatory Response01:28

Inflammatory Response

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.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
19.8K
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...
11.1K
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...
3.5K
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...
10.9K
Chronic Inflammation: Introduction01:12

Chronic Inflammation: Introduction

Chronic inflammation is a prolonged, dysregulated immune response that persists for weeks to years when the inciting stimulus is difficult to eradicate or when self‑antigens drive ongoing reactivity. Morphologically, it is defined by mononuclear cell infiltration, progressive tissue destruction, and concurrent attempts at healing via angiogenesis and fibrosis. Compared with acute inflammation, edema is less prominent while cellular infiltration predominates; triggers include persistent...
4
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.3K