Immunobiology of glomerular diseases
Inflammatory diseases of the kidney filtering units (glomeruli) are a leading cause of chronic renal insufficiency. Despite tremendous advances in our disease understanding, the treatment options remain limited, therefore the investigation of inflammatory processes is of key importance for the development of targeted treatment strategies.
The kidney contains a dense network of immune cells, which is of central importance for organ homeostasis but can also lead to tissue damage and ultimately renal failure. While both kidney biology and renal immunology have made tremendous progress in the past, the interaction between kidney cells like tubulus cells or podocytes and immune cells is still poorly understood.
In the past our group has investigated the proinflammatory properties of podocytes in glomerulonephritis. We are using state-of-the-art live imaging to visualize disease processes and the dynamics of immune cell recruitment to kidney in real-time. Recently, we were able to redefine the function of cDC1 and cDC2 dendritic cells in glomerulonephrits. cDC2, which represent about 90% of DCs in the kidney, have a strong pro-inflammatory function during GN by recruiting Th17 through IL23 and secreting neutrophil-attracting cytokines. In contrast, the cDC1 subset had a robust anti-inflammatory function by counteracting the activity of the cDC2.
We are currently investigating the following areas:
Viehmann, S.F., Bohner, A.M.C., Kurts, C., and Brahler, S. (2018) The multifaceted role of the renal mononuclear phagocyte system. Cell Immunol, 330: 97-104.
Brahler, S., Zinselmeyer, B.H., Raju, S., Nitschke, M., Suleiman, H., Saunders, B.T., Johnson, M.W., Bohner, A.M.C., Viehmann, S.F., Theisen, D.J., Kretzer, N.M., Briseno, C.G., Zaitsev, K., Ornatsky, O., Chang, Q., Carrero, J.A., Kopp, J.B., Artyomov, M.N., Kurts, C., Murphy, K.M., Miner, J.H., and Shaw, A.S. (2018) Opposing Roles of Dendritic Cell Subsets in Experimental GN. J Am Soc Nephrol, 29(1): 138-154.
Yu, H., Artomov, M., Brahler, S., Stander, M.C., Shamsan, G., Sampson, M.G., White, J.M., Kretzler, M., Miner, J.H., Jain, S., Winkler, C.A., Mitra, R.D., Kopp, J.B., Daly, M.J., and Shaw, A.S. (2016) A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis. J Clin Invest, 126(4): 1603.
Brahler, S., Yu, H., Suleiman, H., Krishnan, G.M., Saunders, B.T., Kopp, J.B., Miner, J.H., Zinselmeyer, B.H., and Shaw, A.S. (2016) Intravital and Kidney Slice Imaging of Podocyte Membrane Dynamics. J Am Soc Nephrol, 27(11): 3285-3290.
Brahler, S., Ising, C., Barrera Aranda, B., Hohne, M., Schermer, B., Benzing, T., and Brinkkoetter, P.T. (2015) The NF-kappaB essential modulator (NEMO) controls podocyte cytoskeletal dynamics independently of NF-kappaB. Am J Physiol Renal Physiol, 309(7): F617-26.