The impact of sleep on B cells at the neuroimmune interface

Sleep is essential for physical and mental health. Humans should spend one third of their life asleep. However, modern lifestyles promote constant alertness at the expense of sufficient rest. As a result, the timing and quality of our daily sleep has changed dramatically. This can be attributed to increased work, increased social demands, instant communication and the ease of global travel. Nowadays, more than 35% of Americans sleep fewer than the recommended 7-8 hours per day. In Austria, 46% of adults are estimated to suffer from insufficient sleep with 86% of them having chronic (>6 months) sleep problems. There is substantial clinical evidence that individuals with poor sleep have increased risk of developing disorders, such as cardiovascular diseases (CVD) and autoimmune disorders, like lupus. Despite these associations, we know surprisingly little about the biological pathways and mechanisms that link sleep and disease. In our prior work, we demonstrated that fragmented sleep increases inflammation and accelerates the progression of CVD. We found that disrupted sleep activates the production of inflammatory immune cells in the bone marrow and worsens inflammation in the walls of arteries, a process that leads to heart attacks. Thus, our data showed for the first time how sleep can protect against CVD. In our current research, we are focusing on how sleep influences inflammation in the brain. We propose that one particularly important site in this process are the meninges, a layer of tissue that envelops the brain and serves as an interface between the central nervous system and the periphery. Using innovative preclinical models and technologies we will investigate how sleep changes the function of meningeal immune cells and the clearance of cellular waste products from the brain as well as how these mechanisms impact the development of inflammatory and autoimmune diseases. We will put special emphasis on understanding the role of antibody- producing B lymphocytes in this process, as the dysfunction of these adaptive immune cells largely contributes to both CVD and lupus. This project is a joint effort involving a team of world-renowned scientists and doctors. We will identify new biological pathways by which sleep impacts the immune system. We are well- embedded to translate our findings directly to humans and our studies may lead to the development of novel therapies to treat inflammatory and autoimmune disorders. Our findings will also inform public health policy and support sufficient sleep as an important component of a healthy lifestyle.