There is a growing interest in neuroimmunology, and data suggests that disorders such as Parkinson’s disease and schizophrenia have an autoimmune component.
The ideal disease for studying this phenomenon is, however, the neurologic sleep disorder type 1 narcolepsy (NC), where the hypocretin (hcrt, a neuropeptide also known as orexin) producing neurons in hypothalamus are lost.
Genetic and epidemiological evidence suggest that the specific hcrt cell loss is caused by an autoimmune attack, but the trigger of this is unknown. Research has been limited by few available patient samples collected close to disease onset and a lack of animal models of the autoimmune process.
Autoimmune destruction of neurons
Autoimmune destruction of neurons by cytotoxic T lymphocytes (T cells) is prevented by several mechanisms. Negative selection of autoreactive T cells occurs during T cell maturation in the thymus.
This process is, however, far from perfect and T cells with reactivity towards neuronal targets are instead controlled by other less well-understood mechanisms. These include inhibition of T cell activity by regulatory T cells (T regs), suppression of major histocompatibility complex (MHC) expression in mature neurons under normal conditions, and a higher resistance in neurons to apoptotic signals from T cells.
We hypothesise that some of the proteins genetically associated with narcolepsy plays a role in these processes, and this is what we study. We use both cell culture and animal models. Studies of patient samples collected at the Danish Center for Sleep Medicine translate basic findings to the clinical situation.