Unfolding Brain Autoimmunity
In continuation of the Department of Neuroimmunology (1990-2012), this Extended Emeritus Group is centrally interested in the early events triggering brain specific autoimmune responses, as they are supposed to act in the human inflammatory brain disease, Multiple Sclerosis (MS).
It is established that the immune system of healthy individuals – people as well as animals – contains immune cell clones with receptors for the body’s own tissues, self-reactive T and B cells. These persist in the organism in a dormant, innocuous state. However, when responding to particular stimuli, these cells are awakened to attack their particular target organ. They cause disease: Brain specific T cells, for example, mediate inflammation in the central nervous system (CNS).
Activation of self-reactive T cells was traditionally seen as sequel of infections by pathogenic microbes. Recently, however, we observed an alternative and unexpected triggering process: experimental animal models developed by this group, identified the healthy gut flora as a critical trigger of brain autoimmune disease. We are now following in detail the triggering process as it happens in the intestine and ultimately sets off a cascade of events resulting finally in complex autoimmune inflammation in the brain.
An essential element of our research is the direct observation of early autoimmune interactions in the living animal using cutting-edge real-time imaging approaches. We have adapted two-photon microscopy to retrace the migration of autoimmune lymphocytes from the site of activation through blood circulation, blood-brain barrier into the brain target tissue. These studies now use activation markers developed in-house, which allow not only the observation of migration in the body, but, at the same time indicate the state of activation of each individual cell.
A third core issue of this group is translation of experimental insights to clinical use. In continued close cooperation with the Institute of Clinical Neuroimmunology of the Ludwig Maximilian University (Collaborator: Prof. Dr. Reinhard Hohlfeld, INIM) we have started exploring the role of the gut flora in initiation and course of MS.