Identification of a new mechanism in the immune system provides knowledge about diseases

August 04, 2020

An active immune system protects against diseases and infections. An overactive immune system is the body's worst enemy. One example of this is multiple sclerosis, which is a so-called autoimmune disease, while an overactive immune system also leads to some COVID-19 patients becoming seriously ill.

Now, a research group under the leadership of professor and virologist Søren Riis Paludan from the Department of Biomedicine at Aarhus University, Denmark, has identified a mechanism which is activated in the cells of the immune system when they are attacked by disease. The discovery involves the protein STING, which sends signals to the nucleus of the cell when an infection threatens.

"Until now we've known that the STING protein migrates from an inactive part of the cell to an active when the immune system is alerted, but with this study we can for the first time describe the mechanism that causes the 'migration'. At the same time, we've identified a new protein, STEEP ('STING ER exit protein'), which is responsible for this migration. These are both breakthroughs in terms of understanding the basic disease mechanisms," says Søren Riis Paludan about the study, which has just been published in Nature Immunology.

Previous research has shown that the cells in the immune system are activated through signalling systems organised in what are known as cascades. A system of step-by-step reactions which are e.g. initiated by infection, or when cancer cells are eaten by immune cells. One of these is the cGAS-STING signal cascade, which plays a key role in a number of diseases. The new study shows that STING's 'journey' within the cell trains the activity of the STING signal cascade.

"This part of the process is particularly important because of STING's essential function as part of an innate immune system. The new findings help us to better understand how infectious diseases affect the immune system," says Søren Riis Paludan.

For many years, it has been common knowledge that a well-functioning immune system is extremely important for our health. Even a commonplace infection becomes life-threatening if the immune system is not ready for the fight.

"The immune system is essential in the fight against infection, but if it isn't regulated precisely by the body's own fine-tuning system, it becomes over-activated and creates disease. For example, an overactive immune system has made some COVID-19 patients very ill and difficult to treat," says Søren Riis Paludan.

Identifying the mechanism behind STING's journey and the discovery of the new protein STEEP opens the way to a previously unknown branch in our understanding of the immune system.

"Fundamentally, we're trying to find answers to why in some cases the body's immune system reacts to infections and diseases by causing more illness instead of providing protection. With the STEEP protein, we have a potential source from which we can learn about new principles for how the immune system functions," says Søren Riis Paludan.

Aarhus University

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to