Description of the tasks
The overarching aim of this Work Package is to dissect the common mechanisms by which leukocytes, in particular T cells, macrophages and DCs, and mediators they produce, cont of the cellular immune and autoantibody response rol disease progression, relapses and inflammation-associated organ damage in autoimmune diseases, in particular in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV).
Work Package 4 uses murine models to characterize T cells and to dissect the inflammatory pathways that are controlled by them; investigates how their function is affected by the interaction with dendritic cells and macrophages in tissues; and how infiltrating leukocytes determine tissue injury through secretory mediators. Some of the studies will use humanized mouse lines meaning that they express the human antigens and human immune receptor molecules in the mouse immune system. Partner MONASH has identified overlapping peptide structures in MPO, which are recognized by helper T cells, cytotoxic effector T cells as well as by autoantibody producing B cells. The similarities of these MPO structures between mouse and man are high ensuring the appropriateness and relevance of the model.
Partner HMGU has developed humanized mice, which express the two major antigens, PR3 and MPO, in vasculitis patients. HMGU and MONASH have also developed multiple monoclonal antibodies against the mouse and human antigens, MPO and PR3, which activate human and mouse neutrophils. The RELENT Partners HMGU, MONASH and UKB take advantage of a suite of murine models for inflammatory kidney and lung diseases, using active immunization and passive transfer (of both cells and antibodies) approaches.