The project seeks to reveal the molecular mechanisms controlling the pathogenicity of lymphocytes in multiple sclerosis. For this, mRNA-Seq and a Cre/loxP-based mouse model will be used to analyse the impact of the Th1-associated transcription factor T-bet on the encephalitogenicity of IL-17-producing cells in EAE.
Zusammenfassung der Projektergebnisse
My data on the role of T-bet in Th17 cells show that T-bet contributes to the encephalitogenic potential of Th17 cells but are not the only cell population that determines encephalitogenicity as T-bet deficiency in other Rag1+ T cells also abrogates EAE. It remains to be elucidated how the absence of T-bet decreases EAE symptoms. The mutant mice that are completely resistant to EAE are under intense investigation. Targets from the whole genome sequencing are currently validated and the results from the CD4+ T cell transfer are pending. Depending on these results, I plan to do further adoptive transfers to narrow down the cell population that carries the mutation. After identifying the mutant-carrying cell population I will subject these cells RNA-sequencing. Then, the results will be validated by qPCR, flow cytomertry and transgenic animal models.
