Lymphocytes of the innate and adaptive immune system are central regulators of immune responses in homeostasis and immune-mediated diseases. Recent studies from our group and others have shown that specialized subsets of innate lymphocytes and “innate-like” T cells reside in the kidney and regulate local immune responses. However, the contribution of these innate and innate-like lymphocyte populations to kidney injury and repair in immune-mediated glomerular diseases remains incompletely understood. Preliminary studies by our group suggest that specific interactions between innate-like T cell populations with other immune cells and kidney epithelial cells are crucial for immune regulation in immune-mediated glomerular disease.
By using sc(nuc)RNAseq and spatial tissue analyses (spatial transcriptomics and imaging) we will decipher transcriptional programs and spatial distribution of innate-like T cells and neighboring kidney epithelial cells in different entities of immune-mediated glomerular diseases (ANCA glomerulonephritis, Lupus nephritis, IgA nephropathy). Next, novel complex immune cell – 3D kidney organoid systems will be employed to model kidney diseases in vitro with human cells and investigate the regulation of kidney epithelial cells by innate-like T cells. Finally, selected candidate pathways will be functionally validated in mouse models of glomerulonephritis. In summary, our studies will elucidate the role of innate-like T cells in immune-mediated glomerular diseases and identify targets to develop tailored treatment approaches in patients with glomerulonephritis