Harmful Immune Responses Dampened By Blocking Cytokine IL-21

Mice lacking the receptor for the cytokine IL-21 have less severe symptoms, suggesting that IL-21 is a potential therapeutic target in immune diseases.

AsianScientist (Feb. 18, 2014) – Researchers in Australia have discovered a potential therapeutic target for the treatment of chronic inflammation.

While the initial immune response is necessary to protect the body from infections, prolonged inflammation can lead to a wide array of health problems. In many cases, chronic inflammation is due to an overreaction to ‘self’ tissue (autoimmunity), which in turn can lead to organ damage. The challenge for researchers has been to come up with a way of tuning down the symptoms of chronic inflammation while allowing the body to respond normally to infections.

At Sydney’s Garvan Institute of Medical Research, scientists found that targeting interleukin 21 (IL-21) could be an attractive solution. IL-21 is one of a group of chemical messengers known as ‘cytokines’, which affect the behavior of immune cells. IL-21 is already well known to play an important role in autoimmune diseases such as Sjögren’s syndrome and type 1 diabetes.

Mice lacking another cytokine (IL-2) show symptoms similar to that of chronic inflammation in humans, and are a well-established mouse model of autoimmunity. When IL-2 deficient mice also lacked the receptor for IL-21, they had much less severe symptoms compared to mice with functional IL-21 pathways. This shows that IL-21 contributes to inflammation, and that removal of IL-21 can reduce inflammation, even where other severe immune defects are present.

Associate Professor Cecile King, an author of the study, explains:

“When you remove the IL-2 gene, another group of very calming immune cells known as ‘T regulatory cells’ also disappear – because T regulatory cells express high levels of the IL-2 receptor and are IL-2 dependent. Without T regulatory cells, the immune system goes haywire and the body starts attacking itself.

“Under these conditions, IL-21 kicks in and make things much worse. When IL-21 is blocked, the huge inflammatory response is greatly subdued, although not entirely eliminated. There are many people with chronic inflammation caused by defective T cell regulation, and this research suggests that blocking IL-21 with drugs might help them.”

The full article can be found at: Vogelzang et al. (2014) IL-21 contributes to fatal inflammatory disease in the absence of Foxp3+ T regulatory cells.

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Source: Garvan Institute of Medical Research; Photo: Photo: snre/Flickr/CC.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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