Gp130 cytokines in multiple sclerosis: a role in autoimmunity and remyelination

Abstract

MS is a chronic disabling disease of the CNS, for which current therapies are able to delay disease progression but cannot prevent it. Moreover, for patients in the progressive phase, available therapies largely fail to provide any benefit. Thus, there is an urgent need for novel therapies that can limit and resolve CNS degeneration besides modulating the immune response. Interesting candidates for dual mode therapy are two members of the gp130 cytokine family, namely LIF and OSM. These cytokines can exert similar effects as they both signaling through the LIFR, however human OSM can have additional effects by activating its specific OSMR. In contrast, mouse OSM can only signal through the OSMR, making mice models an excellent tool to selectively study OSMR signaling. In this thesis, the immunomodulatory properties of LIF and OSM were characterized in depth. In addition, the effect of OSM on de‐ and remyelination was investigated. In the following paragraphs, the main findings are summarized and discussed, and suggestions for future research are proposed.