SFB 1192

Project A1

Mechanisms and function of T cell trafficking in crescentic glomerulonephritis

CD4+ T cells orchestrate the immune response and play a unique role in autoimmune and chronic inflammatory diseases. The characterization of TH17 cells, a distinct IL-17 cytokine producing CD4+ T cell subset, has significantly advanced our current understanding of the pathogenic mechanisms of organ-specific immunity. Our group and others have shown that the recruitment of TH17 cells to the inflamed kidney drives renal tissue damage in experimental and possibly human crescentic glomerulonephritis (GN). Despite these advances, the biological functions and signalling pathways of the TH17/IL-17 axis leading to organ injury remain to be fully understood. To achieve this, we have the following aims: 1) Investigation of the mechanisms and function of renal CD4+ T cell trafficking, in particular the molecular events controlling their emigration from (or retention in) the kidney. To this end, we will use mice engineered to express the photoconvertible fluorescent protein, Kaede; 2) Analyses of the TH17/IL-17 cytokine family function, their receptors and their associated chemokines in immune-mediated renal diseases; and 3) High-dimensional analysis of the CD4+ T cell immune response of crescentic GN patients using a systems immunology approach. In summary, continuing this project will result in a better understanding of CD4+ T cell trafficking and of TH17/IL-17 cytokine network involvement in renal autoimmune diseases. These studies are essential to develop pathogenesis-based and personalized treatments to target the TH17/IL-17 pathway.

Publications:

  • IL-17C/IL-17RE: Emergence of a Unique Axis in TH17 Biology.

    Nies JF, Panzer UFront Immunol. 2020 Feb

  • 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

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20246 Hamburg, Germany
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