OTULINVIVO · The role of OTULIN and Met1-linked ubiquitin in immune signaling and host defense in vivo

The role of OTULIN and Met1-linked ubiquitin in immune signaling and host defense in vivo

Every day of our life, we are under attack. Billions of microorganisms (bacteria, viruses, fungi, and parasites) are trying to use our body to find shelter, feed themselves, and reproduce. To fight this never-ending battle, our bodies have developed an effective and complex army: the immune system. The immune system consists of multiple different specialised defence cells collectively called immune cells (or white blood cells). Together, they perform the important defence functions our body needs to prevent the disastrous consequences of uncontrolled infection: detection and destruction of invading microorganisms. The immune system is constantly poised for battle, but it remains at rest until a danger is sensed. It activates when it detects an intruder and immediately starts combatting this microorganism to destroy it. When the invading microorganism has been destroyed, the immune system deactivates and returns to its resting but poised state, ready to combat the next infection. The immune response is a protective measure that is important to keep us healthy and free of infection. But when it goes wrong or is deregulated or uncontrolled it causes the development of a large range of severe and highly disabling diseases, e.g., inflammatory bowel disease, rheumatoid arthritis, diabetes, multiple sclerosis, autoimmune conditions like systemic lupus erythematosus, and skin disorders such as psoriasis, resulting in significant morbidity, reduced quality of life, and premature death for millions of affected individuals worldwide. These immune-mediated diseases are all characterised by uncontrolled and unwarranted activation of the immune system, even in the absence of an infection, causing the cells of the immune system to attack our own body instead of an invading microorganism. This causes acute or chronic inflammation and damage to the affected organ(s). Unfortunately, researchers do not fully understand how these diseases develop, and hence what can be done to treat them. This is in large part because it remains poorly understood how the immune system is regulated and what determines its activation and deactivation in normal and healthy individuals. Therefore, our research aims to investigate the fundamental processes that control the activation and deactivation of the immune system to better understand what goes wrong when the immune system runs amok, activates uncontrollably, and starts to attack our own body. Our hope is that a better understanding of the fundamental biological mechanisms will increase our understanding of the immune-mediated diseases and prompt the development of new and better treatments.

Data: CORDIS, © European Union