The main goal of this project was to gain a better understanding of Chronic Systemic Inflammation (CSI), implicated in several common diseases, such as Psoriasis, Arthritis and Cancer, which are serious health issues. To achieve this goal, we focussed on whole body physiology. As there is no good understanding of the mechanisms behind these diseases, it is important to conduct experiments in model systems, from the petri dish to samples donated by patients. The final aim is to find new ways (biomarkers) to detect these diseases early, when they have the highest chance to be treatable, and to direct the medical community towards new methods to treat and even prevent the disease. We worked along three angles:
1. Inflammatory Skin Diseases (ISD): Atopic Dermatitis (AD) and Psoriasis (Ps) are chronic skin conditions that can lead to a significant deterioration of life quality: 5–30% of children and 2–10% of adults develop AD, while Ps affects 3-5% of the population. AD and Ps are caused by perturbations in the communications between the immune system and keratinocytes, the most important skin cells. We carefully studied how the immune system and the skin interact during ISD, to understand what goes wrong and why. We made several discoveries using our model systems that were communicated to the scientific community and the public. These will certainly help establishing novel biomarkers/treatments that can be further tested and validated in the clinic.
2. Inflammatory Joint Diseases (IJD): Psoriatic Arthritis (PsA) affects up to 30% of Ps patients and leads to joint pain, stiffness and swelling. Debilitating joint degeneration also occurs in Osteoarthritis (OA), the most common joint disease affecting millions of people. OA, where the cartilage is slowly eroded, is a disease affecting the entire joint, with an important role for inflammation. We studied how inflammation/immune system perturbations affect joint degeneration and metabolism in OA and how perturbations in skin-immune system interactions lead to distant effects on the joints in PsA, but also surprisingly in some forms of AD. We discovered important commonalities and differences by comparing different joint diseases and proposed new molecules that could be used as biomarkers after clinical validation. We also made unanticipated discoveries that could be useful for the management of bone cancer (osteosarcoma).
3. Cancer associated Cachexia (CAC): is a disorder of the whole body affecting 50-80% of cancer patients, characterized by involuntary loss of body weight due to wasting of muscles and fat. CAC is detrimental to cancer patients’ quality of life and considered the immediate cause of death for a third of of cancer patients. It is therefore very important to find biomarkers to predict which patient is likely to develop CAC to adapt treatment and lifestyle to prevent or delay cachexia as much as possible. We studied how uncontrolled inflammation, perturbed hormone balance and the nervous system operate and interact during CAC using model systems that mimic the patient situation. We experimentally demonstrated that inflammation and the beta-adrenergic system are important players that should be closely monitored in patients. In addition, we showed how immune cells interact with the sympathetic nervous system during CAC and unravelled unanticipated implications of inflammation in skin and liver cancer. Once validated by clinicians, our findings will likely translate into new biomarkers that will help improve CAC and more generally cancer prevention and treatment.
In conclusion, the CSI-fun project not only allowed us to gain a better understanding of Chronic Systemic Inflammation, but also led to discoveries that will help improve the management of Atopic Dermatitis, Psoriasis, Arthritis and Cancer and decrease the societal burden of these common, but very detrimental diseases.
