Grantor: Croatian Science Foundation
Project duration: 2023. do 2027.
Total funding: 199.037,96 EUR
Project team
Principal investigator:
- doc. dr. sc. Marina Babić Čač dipl. ing. biol.
Research team:
- prof. dr. sc. Astrid Krmpotić, dr. med.
- dr. sc. Daria Kveštak, mag. biol. mol.
Brief description:
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS) associated with inflammation,demyelination, oligodendrocyte loss and axonal injury. It is estimated that MS is the leading cause of nontraumatic neurological disability in 2.5 million young adults In North America and Europe who develop the disease between the ages of 20 and 50 years, Although the causes of MS are still unknown, next to a genetic predisposition, many different environmental factors such as vitamin D deficiency, obesity, smoking, and infection with the Epstein Barr virus (EBV) have been described to play a role in developing MS. Various immune cells have been described to contribute to the inflammatory processes that underlie MS and experimental autoimmune encephalomyelitis (EAE), a mouse model thereof. However, the very early events in this process during MS are still poorly understood. Moreover, the upstream signals that drive the activation as well as multifaceted nature and pathogenicity of these cells as well as the unique features thereof are still poorly defined. Our published and preliminary data suggest that activating receptor NKG2D, as an innate sensor of cellular stress, can modulate effector functlons and impact plasticity of helper T cells during inflammation, however, mechanisms of action are still to be understood. In this project proposal we combine state-of the-art genomics- and sequencing-based technologies in combination with mouse genetic tools and in vivo mouse models of disease to elucidate the contribution of NKG2D / NKG2D-L axis to Th-driven CNS inflammation.