Suppress the immune system

In search of methods of immunity management

Sergey Syrov, XX2 century, based on the materials of the Salk Institute: Curb your immune enthusiasm

It is normal and useful for a healthy body if its immune system quickly and efficiently identifies and destroys the cells affected by the virus. But for scientists who are developing treatment methods based on "therapeutic viruses" (the technology can be used to combat cancer and to correct genetic disorders), excessive activity of the immune system is extremely undesirable. A study conducted at the Salk Institute for Biological Studies shows how the strength of the immune response can be regulated.

The work published on January 19 in the journal Neuron (Tufail et al., Phosphatidylserine Exposure Controls Viral Innate Immune Responses by Microglia) shows that inhibition of the protein PLSCR1 (phospholipid scramblase 1) controls the antiviral response to infected cells and provides their long-term protection from immune attack, protects against excessive inflammation in the area of infection. It is hoped that the results will help in the development of therapy for autoimmune diseases (such as systemic lupus erythematosus) and neurodegenerative disorders (such as Alzheimer's disease).

"Normally, the immune system should quickly recognize and respond to a potential threat, such as a virus–infected cell," says Axel Nimmerjahn, senior author of the publication. "But by acting on PLSCR1, we effectively protect infected cells from immune attack, so that the modified virus continues gene expression for days or weeks, providing long–term therapy."

Therapy with modified viruses is an interesting and promising area of medicine, since it can be used to find and correct disorders at the cellular and molecular level. This is a technology that allows you to target certain cells, for example, tumor cells. However, the immune system does not see any differences between a conventional and a therapeutic virus and the latter must be able to protect.

During the study, scientists injected an altered adenovirus into the mouse brain. The interaction of infected and immune cells was studied, in particular, which proteins are synthesized in response to infection.

Infected cells secrete various substances that are perceived by the body as "distress signals". In particular, it is phosphatidylserine, which activates microglia – specialized immune cells of the brain. Microglia can react differently to an infected cell - kill it or leave it as it is. There can be no single correct reaction – in case of an attack on a cell, nearby brain cells die, if the threat is ignored, the infection can spread to neighboring cells. To understand what signals microglia reacts to in the process of solving the problem of the strength of the response to the threat of infection, the researchers changed the levels of various proteins involved in the process, including phospholipid scramblase 1.

It turned out that suppression of PLSCR1 leads to many changes in the immune response. In particular, the production of cytokines, information molecules that play an important role in inflammatory processes, decreases.

"When we saw how much inhibition of PLSCR1 reduces the inflammatory response, we immediately thought that this mechanism could be used more widely, not only for the introduction of a therapeutic virus into the brain, but also, for example, in the treatment of autoimmune diseases," says Yusuf Tufail, the first author of the publication.

The protective effect of inhibition of PLSCR1 persisted throughout the entire time of its study (up to six months), manipulations with other proteins did not show such a long-term stable result. Since PLSCR1 is present in cells throughout the body, not just in the brain, researchers believe that exposure to it can be used in the treatment of many diseases.

"Given how complex the immune response is and how many genes increase or decrease activity in response to infection, it is surprising that one protein has been found that controls so many signaling pathways," says Professor Nimmerjan. – Imagine a single molecule inhibitor drug that can be used to relieve excessive inflammation. He can save many lives."

Portal "Eternal youth" http://vechnayamolodost.ru  23.01.2017