JUL 06, 2018 01:20 PM PDT

Small Molecules Found to Dial Down Autoimmunity

WRITTEN BY: Carmen Leitch

New drugs are often discovered by studying the effects of small molecules. Scientists have now identified two combinations of these chemicals that can disrupt a cellular pathway that is related to the development of autoimmune disease. Discovered by researchers at EPFL, the work has been reported in Nature

Our body has to defend itself against invaders, and the immune system has a way to identify them and mark them for elimination. One way this is accomplished is by activating a protein called STING (STimulator of Interferon Genes) after microbial DNA has been found by the immune system. STING can then turn other genes on which mount an attack to remove the pathogen.

When this system goes awry, it can turn these defenses against other cells in its own body, an event called autoinflammation (which is described in the video below); it can lead to serious disease. Finding drugs that can prevent this from happening has been extremely challenging, even with all we know about the immune system. 

A research team led by immunologist Andrea Ablasser of EPFL has now found several compounds that can attach to STING, stopping its effects. After screening small molecules to find the ones that lowered the activation of STING, they found two combinations of molecules that can stop STING in human and mouse cells.

The scientists weren’t just looking for an effective chemical, however, they also wanted to know how it was exerting these effects. To learn more, they carefully engineered STING molecules to find exactly which of its amino acids were impacted by the small molecules. This work showed that the small molecules stop a modification from occurring in STING; one of its amino acids, a cysteine residue, can’t be palmitoylated, when palmitic acid is attached. 

Next, the investigators tested the effects of these compounds on autoinflammation. A mouse model of autoinflammatory diseases was used, in which STING is always active. The mice have symptoms that are similar to what humans experience. After those mice were exposed to the small molecule combinations, important markers of autoinflammation were reduced.

In further testing that used human cells growing in culture, a similar impact was seen, and STING was blocked. Clinical trials will be needed to confirm the effects in people with autoimmune diseases, but the researchers are working towards that.
 
“Our work uncovered an unexpected mechanism to target STING and provided the first proof-of-concept that anti-STING therapies are efficacious in autoinflammatory disease,” said Andrea Ablasser. “Beyond specific monogenic autoinflammatory syndromes, the innate immune system is implicated in even broader inflammatory conditions, so we are excited to learn more about the role of STING in human diseases.”

 

Sources: EPFL, Nature

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
JUL 28, 2018
Cell & Molecular Biology
JUL 28, 2018
Self-organizing Synthetic Tissues are Getting More Complex
All the structures in the body arise from a fertilized cell, and scientists are learning more about how that happens....
AUG 05, 2018
Cell & Molecular Biology
AUG 05, 2018
The Major Health Risks Posed by Cipro
In recent years, studies have shown that a once-popular class of antibiotics can have life-threatening side effects....
SEP 04, 2018
Cell & Molecular Biology
SEP 04, 2018
Powerful Imaging Reveals Immune Cells on Patrol
With a tool called lattice light sheet microscopy, scientists can view biological processes as they happen in live cells....
SEP 19, 2018
Cell & Molecular Biology
SEP 19, 2018
A Molecule That Coaxes Muscles to Burn More Fat
Scientists have identified an important molecule that is critical to metabolism....
OCT 06, 2018
Drug Discovery
OCT 06, 2018
New Class of Drugs for Breast Cancer Therapy
Scientists at Stevens Institute of Technology have designed a new class of molecules that may hold the potential to add to the arsenal of drugs actively be...
OCT 09, 2018
Drug Discovery
OCT 09, 2018
'Copper Antibiotic Peptide' Effective in Eradicating Tuberculosis
The bacterium responsible for Tuberculosis has found a way to avoid antibiotics by hiding inside the macrophages which are the specific immune cells that a...
Loading Comments...