Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Inflammatory Bowel Disease III: Crohn's Disease01:25

Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
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...
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...
Autoimmune Disorders01:29

Autoimmune Disorders

Autoimmune diseases are a group of disorders in which the body's immune system mistakenly attacks its own cells, tissues, and organs. This results from an overactive immune response against substances and tissues normally present in the body. Let's delve into the concept and mechanism of autoimmune diseases from an immune system point of view, explore different causes and examples of such diseases, and discuss potential solutions.
Concept and Mechanism of Autoimmune Diseases
The immune system...
Hypersensitivities01:30

Hypersensitivities

Hypersensitivity, also known as a hypersensitivity reaction or allergic reaction, is a condition where the body's immune system reacts abnormally to a foreign substance. Such substances, that cause hypersensitivity are referred to as an allergen, could be something typically harmless to most people, like pollen or certain foods.
Types of Hypersensitivities
Hypersensitivity reactions are categorized into four types: Type 1, Type 2, Type 3, and Type 4. Each type has a distinct mechanism...
Drug Toxicity: Allergic Reactions01:30

Drug Toxicity: Allergic Reactions

Drug-related allergies are immune-mediated responses triggered by the administration of pharmacological agents. These hypersensitivity reactions are classified based on the immune mechanisms involved. The four primary types—Type I, II, III, and IV—are mediated by different immunological pathways and exhibit distinct clinical manifestations.Type I Hypersensitivity/ IgE-Mediated Reactions: Immunoglobulin E (IgE) immediately mediates Type I hypersensitivity reactions. Upon initial exposure to a...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Adult-onset STING-associated vasculopathy.

Journal of human immunity·2026
Same author

Diverse paths to broadly neutralizing antibody escape among HIV-1 strains.

Nature microbiology·2026
Same author

CD14-deficiency protects against osteoarthritic subchondral bone sclerosis via enhanced osteoclastogenesis following joint injury.

bioRxiv : the preprint server for biology·2026
Same author

Neuroimaging Biomarkers of Disease Progression and Cognitive Change in Patients With Retinal Vasculopathy With Cerebral Leukoencephalopathy.

Neurology·2026
Same author

Longitudinal association of retinal morphology and white matter progression in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations.

Frontiers in neurology·2025
Same author

The intersection of TREX1, cGAS, STING and the DNA damage theory of aging.

Frontiers in aging·2025

Related Experiment Video

Updated: Jun 2, 2026

Establishing a Mouse Model of a Pure Small Fiber Neuropathy with the Ultrapotent Agonist of Transient Receptor Potential Vanilloid Type 1
09:39

Establishing a Mouse Model of a Pure Small Fiber Neuropathy with the Ultrapotent Agonist of Transient Receptor Potential Vanilloid Type 1

Published on: February 13, 2018

Autoinflammatory syndromes of STING and TREX1 dysfunction.

Debby J Park1, Kate M Jones1, Jessica B Anderson1

  • 1RVCL Research Center, Department of Medicine.

The Journal of Clinical Investigation
|June 1, 2026
PubMed
Summary

Rare genetic diseases link cytosolic DNA sensing, genome instability, and autoimmunity. Research reveals how TREX1, cGAS, and STING pathways impact these conditions, offering therapeutic avenues.

Related Experiment Videos

Last Updated: Jun 2, 2026

Establishing a Mouse Model of a Pure Small Fiber Neuropathy with the Ultrapotent Agonist of Transient Receptor Potential Vanilloid Type 1
09:39

Establishing a Mouse Model of a Pure Small Fiber Neuropathy with the Ultrapotent Agonist of Transient Receptor Potential Vanilloid Type 1

Published on: February 13, 2018

Area of Science:

  • Genetics
  • Immunology
  • Molecular Biology

Background:

  • Cytosolic DNA sensing via cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) activates innate immunity.
  • The DNA-degrading enzyme three-prime repair exonuclease 1 (TREX1) negatively regulates this pathway; TREX1 loss-of-function causes cytosolic DNA accumulation and STING-mediated autoinflammation.
  • STING gain-of-function mutations lead to STING-associated vasculopathy, a severe multi-organ disease.

Purpose of the Study:

  • To elucidate the complex relationships between cytosolic DNA sensing, genome instability, and autoimmune disease phenotypes.
  • To investigate the role of the TREX1-cGAS-STING pathway in both autoimmune diseases and DNA damage syndromes.
  • To identify potential therapeutic targets for rare genetic disorders.

Main Methods:

  • Review of genetic research on rare diseases.
  • Analysis of molecular mechanisms involving TREX1, cGAS, and STING.
  • Clinical correlation of monogenic autoimmune diseases and DNA damage syndromes.

Main Results:

  • TREX1 deficiency causes cytosolic DNA buildup, leading to STING-driven autoinflammation and autoimmune phenotypes.
  • Aberrant nuclear activity of mislocalized TREX1 causes genomic DNA damage, resulting in multi-organ degeneration and autoimmunity (e.g., retinal vasculopathy with cerebral leukoencephalopathy).
  • The TREX1-cGAS-STING pathway is crucial for both innate immunity regulation and genome stability maintenance.

Conclusions:

  • Monogenic autoimmune diseases and DNA damage syndromes exhibit clinical overlap, highlighting shared molecular pathways.
  • Dysregulation of the TREX1-cGAS-STING pathway is central to several rare genetic disorders.
  • Understanding these pathways opens avenues for developing novel small molecule therapeutics for these debilitating conditions.