Related Experiment Video

Updated: Mar 19, 2026

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
09:51

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

Published on: July 26, 2017

13.1K

Molecular mechanisms of regulation of Toll-like receptor signaling

Cynthia A Leifer1, Andrei E Medvedev2

  • 1Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA; and cal59@cornell.edu.

Journal of Leukocyte Biology
|June 26, 2016
PubMed

Insights

Toll-like receptors (TLRs) are crucial for host defense but can drive autoimmune diseases. This review details TLR regulatory mechanisms and how their dysregulation contributes to inflammatory disorders.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Toll-like receptors (TLRs) are key in detecting pathogens and initiating immune responses.
  • Dysregulated TLR signaling contributes to inflammatory and autoimmune diseases.
  • Nucleic acid-sensing TLRs present unique regulatory challenges due to intracellular localization.

Purpose of the Study:

  • To review the multilayered regulatory mechanisms controlling TLR signaling.
  • To explore how altered TLR regulation contributes to disease pathogenesis.
  • To highlight the specific regulatory aspects of nucleic acid-sensing TLRs.

Main Methods:

  • Literature review of TLR regulation.
  • Analysis of molecular and cellular control mechanisms.
  • Examination of TLRs' role in inflammatory and autoimmune diseases.

Main Results:

  • TLR signaling is tightly controlled by coreceptor interactions, post-translational modifications, trafficking, and negative regulators.
  • Regulation of ligand access, receptor folding, and intracellular transport are critical.
  • Aberrant TLR regulatory mechanisms are implicated in various autoimmune and inflammatory conditions.

Conclusions:

  • Understanding TLR regulatory networks is vital for developing therapies for inflammatory and autoimmune diseases.
  • Targeting specific regulatory pathways offers potential therapeutic strategies.
  • Further research into nucleic acid-sensing TLR regulation is warranted.
Keywords:
inflammationinnate immunitymacrophagespattern recognition receptorssignal transduction

More Related Videos

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces07:55

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

7.9K
Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation09:04

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation

Published on: September 7, 2010

12.0K

Related Concept Videos

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...
10.9K
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
12.4K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
19.0K
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...
10.2K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.7K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.8K