Role of T cell subsets in the pathogenesis of autoimmune blistering disease (C04)

• Subject Area: Dermatology
• Term: since 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246807620

Transfer of autoreactive CD4+ T cells from scurfy mice into T cell-deficient nude mice is sufficient to induce autoantibodies with reactivity to known autoantigens of autoimmune blistering diseases (AIBD). In this project we dissect the initial steps of AIBD-induction by analyzing the impact of different CD4+ T cell subsets for disease induction: We will transfer antigen-specific helper CD4+ T cells, as well as follicular helper T cells (Tfh) from scurfy mice to nude mice and test for induction of autoantibodies as well as clinical signs for AIBD. We will furthermore use this AIBD-model in a therapeutic setting in co-transfer experiments with different types of Treg (iTreg and nTreg). Finally, we will test one newly identified scurfy-derived pathogenic autoantibody for pathogenicity in humans by testing its blister-inducing capacity in human 3D skin models. In summary, these experiments will shed light on the role of various subtypes of CD4+ T cells in the induction of B cell-mediated autoimmune disease and the therapeutic potential of various subtypes of Treg.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 156: The skin as sensor and effector orchestrating local and systemic immunity
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Heads: Professor Dr. Alexander Enk; Professorin Dr. Eva Hadaschik