Role of T cell subsets in anti-glomerular basement membrane glomerulonephritis

Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 101885864

Teilprojekt zu KFO 228: Immunopathogenesis and Therapy of Glomerulonephritis

Autoimmunity against the Goodpasture antigen α3IV-NC1 is the cause of anti-glomerular basement membrane (GBM) glomerulonephritis. Hallmark features are the deposition of autoantibodies along the GBM. Clinical and experimental data also suggest a role for T cells in pathogenesis of disease. Immunization of DBA/1 mice with α3IV-NC1 causes glomerulonephritis with features similar to human anti-GBM disease. In our project, we combine this experimental autoimmune glomerulonephritis (EAG) model with highly sensitive techniques for the analysis of small T cell populations. Our results so far show accumulation of Th1, Th17 and regulatory T cells, including an α3IV-NC1-specific T cell population, in EAG kidneys. However, the role of the different T cell subsets in disease progression is unclear. The project will focus on α3IV-NC1 specific T cells. Specific immunization as well as T cell transfer approaches will be used to determine the role of α3IV-NC1-specific T cell responses in development and progression of EAG. To address the general impact of Th1, Th17 and regulatory T cells, mice deficient in IL-17A, IL-23p19 or IFNγR as well as mice in which regulatory T cells can be specifically depleted were backcrossed onto the DBA/1 background and are now available for analyses in the EAG model. In summary, our results will help to clarify the function of T cells in experimental and human autoimmune GN.