Related Experiment Video

Updated: May 22, 2026

Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
09:51

Development and Functional Characterization of Murine Tolerogenic Dendritic Cells

Published on: May 18, 2018

TLR-activated conventional DCs promote γ-secretase-mediated conditioning of plasmacytoid DCs

Begoña Pérez-Cabezas1, Mar Naranjo-Gómez, Marta Ruiz-Riol

  • 1Laboratori d’Immunobiologia i Diagnòstic Molecular (LIRAD), Banc de Sang i Teixits (BST), Departament de BiologiaCel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Institut d’Investigació Germans Trias i Pujol, Barcelona, Spain.

Journal of Leukocyte Biology
|April 27, 2012
PubMed

Insights

Human dendritic cells (DCs) communicate via cell contact. Activated conventional DCs (cDCs) condition plasmacytoid DCs (pDCs) through Notch signaling, partially activating them for immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Dendritic Cell Biology

Background:

  • Cooperative events between dendritic cell (DC) subsets involve cell contact and soluble factors.
  • In viral infections, murine pDCs induce cDC cooperation via CD40-CD40L and IL-15, while human pDCs use IFN-α.
  • Mechanisms for cDC-induced pDC maturation during bacterial infections were previously undescribed.

Purpose of the Study:

  • To investigate the mechanisms by which human conventional DCs (cDCs) condition plasmacytoid DCs (pDCs).
  • To elucidate the role of cell contact and signaling pathways in DC subset communication.
  • To understand how this interaction influences pDC activation and function.

Main Methods:

  • Sorted human blood-borne cDCs and pDCs from healthy donors.
  • Co-cultured IL-3-maintained pDCs with LPS- or poly(I:C)-activated cDCs.
  • Analyzed pDC maturation markers (CD25, CD86), cytokine/chemokine secretion (IL-6, CCL19), and gene expression, including Notch pathway targets, using inhibitors like DAPT.

Main Results:

  • cDC(LPS)-conditioned pDCs upregulated maturation markers (CD25, CD86) and secreted increased IL-6 and CCL19.
  • Gene expression analysis revealed induction of IL-6, CCL19, and Notch target genes in conditioned pDCs.
  • Inhibition of γ-secretase/Notch pathway (DAPT) reduced Notch target gene expression and CCL19 secretion, indicating cell contact-dependent Notch signaling.

Conclusions:

  • Human cDCs condition pDCs via γ-secretase-mediated mechanisms, including Notch pathway activation.
  • This cell contact-dependent communication results in partial pDC activation.
  • Partially activated pDCs may gain an accessory function contributing to T cell recruitment and activation.

More Related Videos

An Efficient and High Yield Method for Isolation of Mouse Dendritic Cell Subsets09:09

An Efficient and High Yield Method for Isolation of Mouse Dendritic Cell Subsets

Published on: April 18, 2016

A Simple and Efficient Method for Testing Immunomodulatory Agents for Generation of Tolerogenic Dendritic Cells from Human CD14+ Monocytes11:34

A Simple and Efficient Method for Testing Immunomodulatory Agents for Generation of Tolerogenic Dendritic Cells from Human CD14+ Monocytes

Published on: April 11, 2025

Related Concept Videos

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...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
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...
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...
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...