Related Experiment Video

Updated: Jan 29, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

13.2K

Nuclear receptor ligands induce TREM-1 expression on dendritic cells: analysis of their role in tumors

Raffaella Fontana1, Laura Raccosta1, Lucrezia Rovati1

  • 1Immuno-Biotherapy of Melanoma and Solid Tumors Unit, Division of Experimental Oncology, IRCCS Scientific Institute San Raffaele, Milan, Italy.

Oncoimmunology
|February 7, 2019
PubMed

Insights

Nuclear receptor ligands modulate dendritic cell (DC) function, up-regulating TREM-1. This receptor

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Dendritic cells (DCs) are crucial for initiating adaptive immunity via migration to lymphoid organs.
  • Nuclear receptor ligands, such as LXR ligands and 9-cis Retinoic Acid (9-cis RA), can inhibit DC migration by suppressing CCR7 expression.

Purpose of the Study:

  • To investigate the impact of LXR ligand 22R-Hydroxycholesterol (22R-HC) on DC maturation using transcriptomics.
  • To explore the role of nuclear receptor ligands (NRLs) in modulating TREM-1 expression and function in DCs.
  • To assess the involvement of TREM-1+ DCs in cancer and tumor growth.

Main Methods:

  • Transcriptomic analysis of DCs treated with 22R-HC.
  • Testing the effects of various nuclear receptor ligands (NRLs) on TREM-1 expression.
  • Functional assays assessing cytokine release (TNFα, IL-1β) upon TREM-1 triggering.
  • Detection of TREM-1+ DCs in cancer patient samples (pleural effusions, ascites).
  • In vivo studies using Trem-1 bone marrow chimera mice to evaluate tumor growth control.

Main Results:

  • 22R-HC modulated over 1500 genes in maturing DCs, notably up-regulating TREM-1.
  • RXR, RAR, and VDR activation also induced TREM-1 expression.
  • Retinoid-induced TREM-1 triggering enhanced TNFα and IL-1β release.
  • TREM-1+ DCs were detected in cancer patient effusions and ascites.
  • Tumor-conditioned media induced TREM-1 and related target genes in monocyte-derived DCs.
  • Trem-1 deficient mice showed improved control of LLC tumor growth compared to wild-type controls.

Conclusions:

  • Nuclear receptor ligands significantly influence DC function, including the induction of TREM-1.
  • NRL-activated TREM-1+ DCs play a role in inflammation and potentially cancer.
  • TREM-1 expression in DCs is relevant in the tumor microenvironment and impacts tumor growth.
Keywords:
LXR nuclear receptorsRAR/RXR nuclear receptorsTREM-1dendritic cellslung cancerovarian cancer

More Related Videos

A BW Reporter System for Studying Receptor-Ligand Interactions06:05

A BW Reporter System for Studying Receptor-Ligand Interactions

Published on: January 7, 2019

8.1K
Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells10:04

Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells

Published on: August 1, 2025

1.6K

Related Concept Videos

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
618
Internal Receptors01:31

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
74.6K
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
2.5K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.6K
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
8.8K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.5K