A key role for CD4+ T cells as mediators of inflammatory diseases, including glomerulonephritis (GN), has been firmly established. In particular, effector T cells of the T-helper 1 (Th1) and Thelper 17 (Th17) lineages were shown to be highly nephritogenic. On the other hand, regulatory T cells (Treg) have been identified as potent counter regulators of overshooting immune responses and protect from renal tissue injury. Pioneering studies have thus begun to evaluate Treg based therapies for immune mediated diseases. Interestingly, however, it has become clear in the recent past, that Tregs are by no means a uniform population. Rather, highly specialized subtypes of Tregs exist, which are tailor made for the control of a particular type of immune response. Treg1 cells can potently target Th1 and Treg17 cells down regulate Th17 immunity. In addition, a unique Treg subset has been discovered by us and others, which surprisingly expresses the Th17 master transcription factor RORγt and can produce the cytokine IL-17A. These RORγt+ Tregs have been shown to be effector Tregs with enhanced immunosuppressive capacity and potently protect from renal tissue injury. In line with their IL- 17A secretion, however, this unusual Treg population seems to have additional proinflammatory potential. Given their bi-functional nature, we proposed the operational name ´biTregs´. How and under which conditions biTregs exert their pro- and anti-inflammatory functions remains largely unknown to date. In summary, it becomes increasingly evident, that many aspects of the complex Treg biology have not yet been understood. We thus aim to address the following aspects: 1) Characterize the function of endogenous biTregs and identify their mechanisms of action. 2) Analyse the composition of Treg subsets in the blood of patients with Lupus and ANCA associated nephritis. 3) Study the cell type specific role of the chemokine CCL20, which we have in the past identified as a potential effector molecule of biTregs. 4) Evaluate effects of IL-2 receptor (IL-2R) stimulation with a novel mutated human IL-2 protein (´mutein´) on Treg expansion, subset composition and therapeutic potential for GN. Taken together, our studies aim to help advance our understanding of Treg biology and function. The final goal is to establish Treg based therapies for the treatment of GN.