Dissecting sex-specific mechanisms in T cell-mediated autoimmune neuroinflammation

• Applicant: Professor Dr. Manuel A. Friese
• Subject Area: Immunology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 429191104

The pro-inflammatory mechanisms driving the development and progression of multiple sclerosis (MS) show variations between males and females, that need to be considered in immunomodulatory therapy. In our previous project, we discovered the surface protein CD99 to be differentially expressed between male and female T cells in healthy individuals as well as MS patients and demonstrated its functional role in T cell activation and proliferation. In this project proposal, we aim to further disentangle sex differences in T cell-specific pro-inflammatory mechanisms with a focus on chronic neuroinflammation. We therefore created a single cell CITE-Seq dataset of T cells isolated from the central nervous system (CNS) of female and male SJL/J mice during chronic PLP139–151-induced experimental autoimmune encephalomyelitis (EAE), an animal model that depicts key sex differences observed in human MS. In a combined approach by also integrating data from human datasets, we will identify candidates mediating sex differences in pro-inflammatory T cell function that will be mechanistically analysed in vitro and in vivo. Decoding sex-specific aspects of autoimmune neuroinflammation holds the promise for a better pathophysiological understanding of MS and for an individualized, sex-specific therapy.

• DFG Programme: Research Units
• Subproject of: FOR 5068: Sex differences in immunity