Julia Volkmann, MD
Alexandra Helmke, PhD
Janis Casper, MD student
Eva Roy-Chowdhury, MD student
Martina Flechsig, MTA
Tamara Tuchel, BTA
We are interested in the role and regulation of leukocytes in vascular inflammation in renal failure.
Chronic kidney disease affects a large proportion of the population. It impairs host response to pathogens but also increases atherosclerotic inflammation and mortality. Chronic inflammation of the arterial wall is a major contributor to atherosclerotic plaque growth and instability.
We investigate innate immune cells and the vascular inflammatory infiltrate in patients with chronic kidney disease and mouse models of atherosclerosis. A focus of our work has been the role of the T cell cytokine Interleukin 17 in regulation of innate immune cells (Ge et al., 2013, Dong et al, 2016, Nordlohne et al., 2018).
Innate leukocytes, especially neutrophilic granulocytes and monocytes and macrophages in uremia are studied also in other conditions.
For example, we have investigated kidney macrophages after transplantation and correlated their abundance with transplant survival and complications such as urinary tract infections.
Peritoneal dialysis is an important mode of renal replacement therapy. It can be a successful for years or fail due to peritoneal membrane thickening and inflammatory changes. We use our immunologic interest to better understand macrophages crosstalk with the peritoneal membrane.
In summary, we aim to improve mechanistic understanding of innate inflammation in renal impairment with the goal to define specific treatment avenues.
Our work is supported by
Deutsche Forschungsgemeinschaft, Else Kröner Fresenius Stiftung, IfBtx and others
1. Helmke A*, Nordlohne J*, Balzer MS, Dong L, Rong S, Hiss M, Shushakova N, Haller H von Vietinghoff, S. CX3CL1-CX3CR1 interaction mediates macrophage-mesothelial crosstalk that promotes peritoneal fibrosis in vivo. Kidney international in press 2019, doi.org/10.1016/j.kint.2018.12.030.
2. Helmke A, Casper J, Nordlohne J, David S, Haller H, Zeisberg E, von Vietinghoff S. Endothelial-to-mesenchymal transition shapes the atherosclerotic plaque and modulates macrophage function. FASEB J. 2019 Feb;33(2):2278-2289.
3. Casper J*, Schmitz J*, Bräsen JH, Khalifa A, Schmidt BMW, Einecke G, Haller H, von Vietinghoff S. Renal transplant recipients receiving loop diuretic therapy have increased urinary tract infection rate and altered medullary macrophage polarization marker expression. Kidney International 2018 Nov;94(5):993-1001.
4. Nordlohne J, Helmke A, Ge S, Rong S, Chen R, Waisman A, Haller H, von Vietinghoff, S. Aggravated atherosclerosis and vascular inflammation with reduced kidney function depend on Interleukin-17 receptor A and are normalized by inhibition of IL-17A. JACC Basic to translational Science Jan 2018 doi.org/10.1016/j.jacbts.2017.08.005
5. Bräsen JH, Khalifa A, Schmitz J, Dai W, Einecke G, Schwarz A, Hallensleben M, Schmidt BMW, Kreipe HH, Haller H, von Vietinghoff S. Macrophage density in early surveillance biopsies predicts future renal transplant function. Kidney international 2017 Aug;92(2):479-489.
6. Dong L, Helmke A, Waisman A, Haller H, Pich A, von Vietinghoff S. Surface-bound bovine serum albumin carrier protein as present in recombinant cytokine preparations amplifies T helper 17 cell polarization. Sci Rep. 2016 Nov 3;6:36598.
7. Dong L*, Nordlohne J*, Ge S, Hertel B, Melk A, Rong S, Haller H, von Vietinghoff S. T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal Impairment. J Am Soc Nephrol. 2016 Jun;27(6):1753-64.
8. Ge S, Hertel B, Koltsova EK, Sörensen-Zender I, Kielstein JT, Ley K, Haller H, von Vietinghoff S. Increased atherosclerotic lesion formation and vascular leukocyte accumulation in renal impairment are mediated by Interleukin 17A. Circ Res. 2013 Sep 27;113(8):965-74.