Center for Molecular Medicine Cologne

Sebastian Brähler - CAP 17

Immunobiology of glomerular diseases

Introduction

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:

  1. Characterization of the anti-inflammatory properties of cDC1 and checkpoint proteins: Based on our recent data, cDC1 have robust anti-inflammatory properties in glomerulonephritis. Therefore, we use kidney disease models, flow cytometry and advanced imaging methods to understand their exact molecular function.
  2. Analysis of glomerular pro-inflammatory signaling: Glomerulonephritis is a specific inflammation of the renal filtering unit. Renal cells like podocytes are among the first responders to tissue injury. We analyze and try to modulate the inflammatory environment in glomeruli to prevent disease progression right where it starts.
  3. Immune cell metabolism in renal diseases. Metabolism is a fundamental prerequisite for each cell’s activation and function. Our aim is to investigate the involvement of key metabolic pathways in renal disease like the TCA cycle.
  1. Völker LA, Kaufeld J, Miesbach W,Brähler S, Reinhardt M, Kühne L, Mühlfeld A, Schreiber A, Gaedeke J, Tölle M, Jabs WJ, Özcan F, Markau S, Girndt M, Bauer F, Westhoff TH, Felten H, Hausberg M, Brand M, Gerth J, Bieringer M, Bommer M, Zschiedrich S, Schneider J, Elitok S, Gawlik A, Gäckler A, Kribben A, Schwenger V, Schoenermarck U, Roeder M, Radermacher J, Bramstedt J, Morgner A, Herbst R, Harth A, Potthoff SA, von Auer C, Wendt R, Christ H, Brinkkoetter PT, Menne J. ADAMTS13 and VWF Activities Guide Individualized Caplacizumab Treatment in Patients With aTTP, Blood Adv. 2020 Jul 14;4(13):3093-3101.
     
  2. Viehmann SF, Böhner AMC, Kurts C, Brähler S., The multifaceted role of the renal mononuclear phagocyte system, Cell Immunol. 2018 Aug;330:97-104. Review
     
  3. Brähler S, Zinselmeyer BH, Raju S, Nitschke M, Suleiman H, Saunders BT, Johnson MW, Böhner AMC, Viehmann SF, Theisen DJ, Kretzer NM, Briseño CG, Zaitsev K, Ornatsky O, Chang Q, Carrero JA, Kopp JB, Artyomov MN, Kurts C, Murphy KM, Miner JH, Shaw AS, Opposing Roles of Dendritic Cell Subsets in Experimental GN. J. Am. Soc. Nephrol. 29: 138–154, 2018
     
  4. Koehler S*, Brähler S*, Braun F, Hagmann H, Rinschen M, Höhne M, Wunderlich T,  SchermerB, Benzing T, Brinkkoetter PT, A T2A-peptide based knock-in mouse model for enhanced Cre recombinase activity and fluorescent labeling of podocytes Kidney International Kidney Int. 2017 Jun;91(6):1510-1517.
  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  • Volker LA, Kaufeld J, Miesbach W, Brahler S, Reinhardt M, Kuhne L, Muhlfeld A, Schreiber A, Gaedeke J, Tolle M, Jabs WJ, Ozcan F, Markau S, Girndt M, Bauer F, Westhoff TH, Felten H, Hausberg M, Brand M, Gerth J, Bieringer M, Bommer M, Zschiedrich S, Schneider J, Elitok S, Gawlik A, Gackler A, Kribben A, Schwenger V, Schoenermarck U, Roeder M, Radermacher J, Bramstedt J, Morgner A, Herbst R, Harth A, Potthoff SA, von Auer C, Wendt R, Christ H, Brinkkoetter PT, and Menne J (2020b). ADAMTS13 and VWF activities guide individualized caplacizumab treatment in patients with aTTP. Blood advances 4, 3093-101.
Dr. med. Sebastian Brähler CMMC Cologne
Dr. med. Sebastian Brähler

Clinic II of Internal Medicine

Principal Investigator CAP 17

Co-Principal Investigator - B 01

RG location - CMMC Building

+49 221 478 96978

Clinic II of Internal Medicine

Robert-Koch-Str. 21

50931 Cologne

https://www.kidneyresearchcenter.org/1/Home.htm

CMMC Profile Page

Curriculum Vitae (CV)

Publications on PubMed

Publications - Sebastian Brähler

Link to PubMed