Jun. Prof. Dr. med. Ingo Kleiter, Neuroimmunologisches Labor

Ingo Kleiter

Research Programme:

Multiple sclerosis (MS) is an autoimmune inflammatory and degenerative disease of the CNS. For unknown reasons its incidence and female preponderance are increasing in the western hemisphere, which suggests that environmental factors, in particular changes in lifestyle contribute to MS pathogenesis. While a genetic predisposition mainly affecting immune cell function was verified in many studies, it is still unknown where and how the immune process is initiated. Referring to both unsolved questions, a new pathogenetic concept was recently proposed. According to this idea, the commensal gut flora which lives in symbiosis with the host and is also called microbiome shapes the development and function of the intestinal immune system, and can cause inflammatory autoimmune diseases in the gut and the rest of the body.

We hypothesize that changes in the microbiome lead to a dysregulated immune response in the gut and predispose to activation of self-reactive T cells capable of inducing tissue damage in the CNS. In particular, we want to examine whether gut immune processes are altered during MS. Several models of autoimmune CNS inflammation and therapeutic modulation of these models will be used. In addition, studies with biomaterial from MS patients will be done.

Another daunting clinical problem of MS is how to stop the underlying neurodegeneration which starts early in the course of disease. Brain atrophy increases with age in MS patients at a much higher rate than in healthy controls. Cognitive impairment is frequent, may occur early and may progress throughout the disease course. Recently, it became evident that the adult brain has an intrinsic self-repair mechanism, so called neuronal stem cells. However, neuroregenerative mechanisms seem to be blunted in MS. Finding neuroprotective or even neuroregenerative therapies is therefore an important goal of MS research.

We are interested to know whether established and emerging drugs for MS also have neuroregenerative modes of action apart from their immunomodulatory effects. We use several in vivo and in vitro paradigms to characterize the proliferation and differentiation of neuronal stem cells under defined conditions and to test for functional consequences.

PhD projects will be available in both topics.