SFB 1192

Project A1

Mechanisms and function of T cell trafficking in crescentic glomerulonephritis

CD4+ T cells play a unique role in the pathogenesis of autoimmune disease, including human and experimental crescentic glomerulonephritis (GN). To exert their distinct effector functions, CD4+ T cells have to migrate into the target organ. Our group and others have shown that the recruitment of TH1 and TH17 cells to the inflamed kidney drives renal tissue damage, while regulatory T cells (Tregs) suppress overwhelming and destructive immune responses. Chemokines and their receptors have been identified as key regulators of directional leukocyte migration. However, the precise role of these molecule families in T cell subset trafficking and autoimmune tissue injury remains to be fully elucidated. In this project, we will address the following issues:

  1. Mechanisms and function of T cell trafficking into and out of the kidney.
  1. Analysis of the TH17/IL-17 cytokine family, their receptors and their relation to the chemokine system in renal inflammation.
  1. Characterization of the renal and systemic CD4+ T cell immune response in patients with crescentic GN by using flow cytometric and immunohistochemical techniques.

In summary, our studies will result in a better understanding of chemokine/chemokine receptor-regulated TH1, TH17, and Treg-cell trafficking and of the involvement of these T cell subsets (and their cytokines) in renal autoimmunity. These studies are the prerequisite for developing pathogenesis-based anti-cytokine treatment strategies.

Publications:

  • IL-17C/IL-17 Receptor E Signaling in CD4+ T Cells Promotes TH17 Cell-Driven Glomerular Inflammation. 

    Krohn S, Nies JF, Kapffer S, Schmidt T, Riedel JH, Kaffke A, Peters A, Borchers A, Steinmetz OM, Krebs CF, Turner JE, Brix SR, Paust HJ, Stahl RAK, Panzer UJ Am Soc Nephrol. 2018 Apr

  • Tissue-Resident Lymphocytes in the Kidney. 

    Turner JE, Becker M, Mittrücker HW, Panzer UJ Am Soc Nephrol. 2018 Feb

  • T helper type 17 cells in immune-mediated glomerular disease

    Krebs C, Schmidt T, Riedel J, Panzer U Nat Rev Nephrol. 2017 Oct

  • Autoimmune Renal Disease Is Exacerbated by S1P-Receptor-1-Dependent Intestinal Th17 Cell Migration to the Kidney. 

    Krebs CF, Paust HJ, Krohn S, Koyro T, Brix SR, Riedel JH, Bartsch P, Wiech T, Meyer-Schwesinger C, Huang J, Fischer N, Busch P, Mittrücker HW, Steinhoff U, Stockinger B, Perez LG, Wenzel UO, Janneck M, Steinmetz OM, Gagliani N, Stahl RA, Huber S, Turner JE, Panzer U.Immunity. 2016 Nov

  • Plasticity of Th17 Cells in Autoimmune Kidney Diseases. 

    Krebs CF, Turner JE, Paust HJ, Kapffer S, Koyro T, Krohn S, Ufer F, Friese MA, Flavell RA, Stockinger B, Steinmetz OM, Stahl RA, Huber S, Panzer UJ Immunol. 2016 Jul

  • IL-17F Promotes Tissue Injury in Autoimmune Kidney Diseases

    Riedel J, Paust H, Krohn S, Turner J, Kluger M, Steinmetz O, Krebs C, Stahl R, Panzer U J Am Soc Nephrol. 2016 Dec

III. Medizinische Klinik und Poliklinik
Universitätsklinikum Hamburg-Eppendorf

Martinistrasse 52
20246 Hamburg, Germany
Tel:   +49-40-7410-51557
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