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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.


  • CD4+ T cells produce GM-CSF and drive immune-mediated glomerular disease by licensing monocyte-derived cells to produce MMP12.

    Hans-Joachim Paust, Ning Song, Donatella De Feo, Nariaki Asada, Selma Tuzlak, Yu Zhao, Jan-Hendrik Riedel, Malte Hellmig, Amirrtavarshni Sivayoganathan, Anett Peters, Anna Kaffke, Alina Borchers, Ulrich O Wenzel, Oliver M Steinmetz, Gisa Tiegs, Elisabeth Meister, Matthias Mack, Christian Kurts, Sibylle von Vietinghoff, Maja T Lindenmeyer, Elion Hoxha, Rolf A K Stahl, Tobias B Huber, Stefan Bonn, Catherine Meyer-Schwesinger, Thorsten Wiech, Jan-Eric Turner, Burkhard Becher, Christian F Krebs, Ulf PanzerSci Transl Med. 2023 Mar

  • Glucocorticoids target the CXCL9/CXCL10-CXCR3 axis and confer protection against immune-mediated kidney injury.

    Jan-Hendrik Riedel, Lennart Robben, Hans-Joachim Paust, Yu Zhao, Nariaki Asada, Ning Song, Anett Peters, Anna Kaffke, Alina Borchers, Gisa Tiegs, Larissa Seifert, Nicola M Tomas, Elion Hoxha, Ulrich O Wenzel, Tobias B Huber, Thorsten Wiech, Jan-Eric Turner, Christian F Krebs, Ulf PanzerJCI Insight. 2023 Jan

  • IL-17 Receptor C Signaling Controls CD4+ TH17 Immune Responses and Tissue Injury in Immune-Mediated Kidney Diseases.

    Schmidt T, Luebbe J, Kilian C, Riedel JH, Hiekmann S, Asada N, Ginsberg P, Robben L, Song N, Kaffke A, Peters A, Borchers A, Flavell RA, Gagliani N, Pelzcar P, Huber S, Huber TB, Turner JE, Paust HJ, Krebs CF, Panzer U.J Am Soc Nephrol. 2021 Dec

  • Neutralization of IL-6 inhibits formation of autoreactive TH17 cells but does not prevent loss of renal function in experimental autoimmune glomerulonephritis.

    Brede KM, Schmid J, Steinmetz OM, Panzer U, Klinge S, Mittrücker HW.Immuno Lett. 2021 Aug

  • Tissue-specific therapy in immune-mediated kidney diseases: new ARGuments for targeting the IL-23/IL-17 axis.

    Krebs CF, Tuner JE, Riedel JH, Panzer UJ Clin Invest. 2021 Jun

  • A fetal wave of human type 3 effector γδ cells with restricted TCR diversity persists into adulthood.

    Likai Tan, Alina Suzann Fichtner, Elena Bruni, Ivan Odak, Inga Sandrock, Anja Bubke, Alina Borchers, Christian Schultze-Florey, Christian Koenecke, Reinhold Förster, Michael Jarek, Constantin von Kaisenberg, Ansgar Schulz, Xiaojing Chu, Bowen Zhang, Yang Li, Ulf Panzer, Christian F Krebs, Sarina Ravens, Immo Prinz Sci Immunol. 2021 Apr

  • Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients.

    Yu Zhao, Christoph Kilian, Jan-Eric Turner, Lidia Bosurgi, Kevin Roedl, Patricia Bartsch, Ann-Christin Gnirck, Filippo Cortesi, Christoph Schultheiß, Malte Hellmig, Leon U B Enk, Fabian Hausmann, Alina Borchers , Milagros N Wong, Hans-Joachim Paust , Francesco Siracusa, Nicola Scheibel, Marissa Herrmann, Elisa Rosati, Petra Bacher , Dominik Kylies, Dominik Jarczak, Marc Lütgehetmann, Susanne Pfefferle, Stefan Steurer, Julian Schulze Zur-Wiesch, Victor G Puelles, Jan-Peter Sperhake, Marylyn M Addo, Ansgar W Lohse, Mascha Binder, Samuel Huber, Tobias B Huber, Stefan Kluge, Stefan Bonn, Ulf Panzer , Nicola Gagliani, Christian F Krebs.Sci Immunol. 2021 Feb

  • Pathogen-induced tissue-resident memory TH17 (TRM17) cells amplify autoimmune kidney disease.

    Krebs CF, Reimers D, Zhao Y, Paust HJ, Bartsch P, Nuñez S, Rosemblatt MV, Hellmig M, Kilian C, Borchers A, Enk LUB, Zinke M, Becker M, Schmid J, Klinge S, Wong MN, Puelles VG, Schmidt C, Bertram T, Stumpf N, Hoxha E, Meyer-Schwesinger C, Lindenmeyer MT, Cohen CD, Rink M, Kurts C, Franzenburg S, Koch-Nolte F, Turner JE, Riedel JH, Huber S, Gagliani N, Huber TB, Wiech T, Rohde H, Bono MR, Bonn S, Panzer U, Mittrücker HW.Sci Immunol. 2020 Aug

  • Neutrophil Gelatinase-Associated Lipocalin Protects from ANCA-Induced GN by Inhibiting TH17 Immunity.

    Adrian Schreiber, Anthony Rousselle, Jan Klocke, Sebastian Bachmann, Suncica Popovic, Julia Bontscho, Kai M Schmidt-Ott, Volker Siffrin, Uwe Jerke, Muhammad Imtiaz Ashraf, Ulf Panzer, Ralph KettritzJ Am Soc Nephrol. 2020 Jul

  • Kidney dendritic cells: fundamental biology and functional roles in health and disease.

    Kurts C, Ginhoux F, Panzer UNat Rev Nephrol. 2020 Jul

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

    Christian F Krebs, Hans-Joachim Paust, Sonja Krohn, Tobias Koyro, Silke R Brix, Jan-Hendrik Riedel, Patricia Bartsch, Thorsten Wiech, Catherine Meyer-Schwesinger, Jiabin Huang, Nicole Fischer, Philipp Busch, Hans-Willi Mittrücker, Ulrich Steinhoff, Brigitta Stockinger, Laura Garcia Perez , Ulrich O Wenzel, Matthias Janneck, Oliver M Steinmetz, Nicola Gagliani, Rolf A K Stahl, Samuel Huber, Jan-Eric Turner, Ulf PanzerImmunity. 2016 Nov