A pathogen-specific CD4 T cell atlas for chronic inflammatory diseases

• Applicants: Professorin Dr. Petra Bacher; Professor Dr. Andre Franke; Professor Dr. Alexander Scheffold
• Subject Area: Immunology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 433038070

Chronic-inflammatory diseases (CIDs) at barrier tissues are linked to pathogenic reactions of the immune system against microbiota. However, CIDs represent a heterogenous group of diseases determined by multiple genetic parameters, modulation of the microbiota composition and further environmental factors, which altogether affect host-microbiota interaction. Thus, for understanding of disease etiology and personalized therapy development it is an intriguing option to stratify patients according to their pathogenic immune signatures, i.e. the specific microbial immune targets and the quality of the immune reaction. Current diagnostic approaches cannot resolve microbiota-specific T cell response patterns. However recent technologies developed by our labs allow accessing and deep molecular profiling of microbiota-specific human T cells and identified key immune targets. Thus, we propose to generate a human microbe-specific T cell atlas to define prototypic pathogenic immune signatures and correlate them with genetic variants, microbial colonization and clinical disease parameters. We further aim to decipher the molecular and cellular mechanism of altered immune reactivity. Our project shall provide a basis to understand the connection of genetic and immunological parameters for individual CID patients and to develop improved personalized therapeutic strategies.

• DFG Programme: Research Grants