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:
Koehler S*, Brähler S*, Kuczkowski A, Binz J, Hackl MJ, Hagmann H, Höhne M, Vogt MC, Wunderlich CM, Wunderlich FT, Schweda F, Schermer B, Benzing T, Brinkkoetter PT., Single and Transient Ca2+ Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion.Sci Rep. 2016 Oct 19;6:35400.
Brähler S*, Yu H*, Suleiman H, Krishnan GM, Saunders BT, Kopp JB, Miner JH, Zinselmeyer BH, Shaw AS. Intravital and kidney slice imaging of podocyte membrane dynamics. J Am Soc Nephrol. 2016 Apr 1.
Yu H*, Artomov M*, Brähler S*, Stander MC, Shamsan G, Sampson MG, White JM, Kretzler M, Miner JH, Jain S, Winkler CA, Mitra RD, Kopp JB, Daly MJ, Shaw AS. A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis. J Clin Invest. 2016 Mar 1;126(3):1067-78.
Brähler S*, Ising C*, Barrera Aranda B, Höhne M, Schermer B, Benzing T, Brinkkoetter PT. The NF-κB essential modulator (NEMO) controls podocyte cytoskeletal dynamics independently of NF-κB. Am J Physiol Renal Physiol. 2015 Oct 1;309(7):F617-26.
Brähler S, Ising C, Hagmann H, Rasmus M, Hoehne M, Kurschat C, Kisner T, Goebel H, Shankland S, Addicks K, Thaiss F, Schermer B, Pasparakis M, Benzing T, Brinkkoetter PT. Am J Physiol Renal Physiol. 2012 Nov 15;303(10):F1473-85
Brähler S, Kaistha A, Schmidt VJ, Wölfle SE, Busch C, Kaistha BP, Kacik M, Hasenau AL, Grgic I, Si H, Bond CT, Adelman JP, Wulff H, de Wit C, Hoyer J, Köhler R. Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension Circulation. 2009 May 5;119(17):2323-32.
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