Related Experiment Video

Updated: May 2, 2026

Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
07:17

Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice

Published on: June 22, 2016

9.5K

STAT3 activation by KSHV correlates with IL-10, IL-6 and IL-23 release and an autophagic block in dendritic cells

Roberta Santarelli1, Roberta Gonnella1, Giulia Di Giovenale1

  • 1Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy.

Scientific Reports
|March 1, 2014
PubMed

Insights

Kaposi's sarcoma-associated herpesvirus (KSHV) activates STAT3 in dendritic cells (DCs), leading to cytokine release and blocked autophagy. Inhibiting STAT3 restores DC function, revealing a key mechanism in KSHV-induced immune dysfunction.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Kaposi's sarcoma-associated herpesvirus (KSHV) infects immune cells like monocytes and dendritic cells (DCs), impairing their function.
  • The precise molecular mechanisms behind KSHV-induced immune cell dysfunction are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which KSHV impairs dendritic cell (DC) function.
  • To investigate the role of STAT3 activation and autophagy in KSHV-infected DCs.

Main Methods:

  • Exposure of dendritic cells (DCs) to active or UV-inactivated KSHV.
  • Analysis of STAT3 phosphorylation, cytokine release (IL-10, IL-6, IL-23), and autophagy markers (LC3II, p62).
  • Assessment of the effects of STAT3 inhibition on DC function and cytokine production.

Main Results:

  • KSHV exposure induced STAT3 phosphorylation in DCs, partially dependent on DC-SIGN engagement.
  • Activated STAT3 promoted the release of IL-10, IL-6, and IL-23, creating a feedback loop for sustained STAT3 activation.
  • STAT3 activation correlated with impaired autophagy in DCs, evidenced by reduced LC3II and increased p62.
  • Inhibition of STAT3 activation reversed the cytokine release and the autophagic block.

Conclusions:

  • STAT3 activation is a key molecular mechanism underlying KSHV-mediated dendritic cell (DC) dysfunction.
  • This STAT3-driven dysfunction, characterized by cytokine release and impaired autophagy, may facilitate KSHV persistence.
  • The findings suggest a link between KSHV-induced DC dysfunction, viral persistence, and the development of KSHV-associated malignancies.

More Related Videos

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

7.6K
siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells09:10

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells

Published on: October 28, 2019

9.1K

Related Concept Videos

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...
3.2K
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...
10.2K
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
2.4K
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...
14.4K
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...
13.7K