Project R-15910

T cell palmitoylation as functional regulator of immunity in multiple sclerosis (Research)

Increasing evidence indicates that fatty acid metabolism drives immune cell function and differentiation in autoimmune disorders such as multiple sclerosis (MS). However, the culprit fatty acids and molecular mechanisms that govern the impact of fatty acid metabolism on immune cell function and the disease pathology remain poorly understood. The saturated fatty acid palmitate is the most common fatty acid in the human body and is situated at the heart of fatty acid metabolism. While our research group and others found that subtle changes in intracellular levels of palmitate have a major impact on immune cell function and MS disease pathology, the mode of action is unclear. In this project, I will define if protein S-palmitoylation, a post-translational modification that consists of the reversible addition of palmitate to proteins, drives T cell (dys)function in MS. Ever since its discovery, it has become evident that S-palmitoylation is essential in controlling protein function and cellular physiology, and that disturbances in S-palmitoylation are implicated in the pathogenesis of autoimmune diseases, cancer, and metabolic disorders. Findings from this project will lead to increased insight into the role of S-palmitoylation in T cell differentiation and MS pathology and will unravel the therapeutic applicability of S-palmitoylation modulators to dampen autoimmunity.

01 November 2025 - 31 October 2027