Functional genetics of sex differences in autoimmunity

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

Differences in the immune response between women and men are leading to a strong sex bias in the incidence of autoimmune diseases that predominantly affect females. This has been docu-mented for many autoimmune diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis, autoimmune liver diseases – and for multiple sclerosis (MS). MS is the most common inflammatory disease of the central nervous system (CNS) and manifests in more than twice as many women, making sex one of the top risk factors for developing MS. Various factors can contribute to sex differences, such as hormones, genetic or epigenetic factors, which can influ-ence immune cell function. However, it is unknown which genes are differentially expressed in females and males and could thereby contribute to sex differences in autoimmune incidence. To address that we conducted a gene expression analysis in female and male human spleen and blood using the Genotype-Tissue Expression (GTEx) project dataset. From 62 differentially ex-pressed genes (DEGs) in the blood and 114 DEGs in the spleen, we selected DEGs that had associations with immune regulation. After successful validation of the transmembrane protein CD99, which is markedly increased in men, we will here focus on its sex-specific contribution to T cell activation and transmigration. We hypothesize that sex determines expression of CD99 resulting in different immune cell responses in females and males. This emerging sex-specific expression and functional differences could contribute to sexual disparity in autoimmunity, such as MS.

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