Modeling a complex disease: Multiple sclerosis-Update 2020.

Multiple sclerosis (MS) is a complex inflammatory disease of the central nervous system (CNS) with an unknown etiology. Thereby, MS is not a uniform disease but rather represents a spectrum of disorders, where each aspect needs to be modeled with specific requirements-for a systematic overview see our previous issue of this review (Kurschus, Wortge, & Waisman, 2011). However, there is broad consensus about the critical involvement of the immune system in the disease pathogenesis. To better understand how the immune system contributes to CNS autoimmunity, the model of experimental autoimmune encephalomyelitis (EAE) was developed. EAE can be induced in susceptible animals in many different ways, with the most popular protocol involving the activation of self-reactive T cells by a peptide based on the myelin oligodendrocyte glycoprotein sequence. In the last 10 years this model has led to major advances in our understanding of the immune system, especially the nature of IL-17-producing T cells (Th17 cells), host-microbiome interactions, the gut-brain axis and how the immune system can cause damage in different regions of the brain and the spinal cord. This update summarizes some of the main achievements in the field in the last 10 years.