Masters Thesis

Validation of EBI2 as a novel therapeutic target for autoimmune disorders

The G protein-coupled receptor (GPCR) Epstein-Barr virus-induced protein 2 (EBI2) has no known natural/endogenous ligand or activator. EBI2 could potentially have an important function in the human immune system due to its high expression in immune cells. It also shows high expression in psoriatic lesions in comparison to healthy skin perhaps indicating a role during inflammatory responses in the skin. We have demonstrated that EBI2 is involved in the toll-like receptor dependent in vitro modulation of proinflammatory cytokines and chemokine in monocyte-derived dendritic cells (MDDC). T cells from EBI2-KO mouse showed no defect in ex vivo proliferation. The EBI2-KO mouse was tested in three autoimmune disease models. In the psoriasis model, DNFB induced skin inflammation, no effect was observed on the adaptive immune response. There was a trend in the innate immune response where EBI2-KO mice showed less inflammation. In the multiple sclerosis model, MOG induced EAE, no distinguishable difference was observed between the EBI2-KO and the wild type animals. In the DSS induced colitis we saw no differences between the knock out and wild type groups. In sum EBI2 does not appear to be indispensable to the development of the autoimmune disorder animal models tested. Further studies are required to fully understand the role of this highly and specifically expressed GPCR in the immune system.

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