SFB 1192

Project A4

Autoreactive T cell responses in glomerulonephritis

Immune-mediated glomerular diseases result from adaptive responses against glomerular structures or responses against circulating soluble or cellular antigens which manifest in the glomeruli. Anti-glomerular basement membrane (GBM) glomerulonephritis (GN) is caused by immunity against the Goodpasture antigen α3IV-NC1. Formation and renal deposition of anti-α3IV-NC1 IgG are central events leading to manifestation of anti-GBM GN. However, clinical and experimental evidence also suggest a fundamental role for T cells in disease pathogenesis.

Immunization of DBA/1 mice with α3IV-NC1 causes crescentic GN with features similar to anti-GBM disease. In this experimental autoimmune glomerulonephritis (EAG), we can identify α3IV-NC1-specific CD4+ TH1 and TH17 cells in inflamed kidneys. Our results further indicate that both TH1 and TH17 cells participate in the formation of necrotizing/crescentic GN. The current project therefore has two main focuses. The first aim is to characterize mechanisms that control autoreactive T cells and progression of renal disease to crescentic GN in EAG. We will determine the impact of regulatory T cells as well as of IL-6, a central regulator of inflammation, in this process. The second aim is to characterize autoreactive CD4+ T cells in human glomerular diseases. In cooperation with the Hamburg GN Registry, we will apply our sensitive assays developed for detection of α3IV-NC1-specific CD4+ T cells in EAG for the identification and characterization of PLA2R1- and THSD7A-specific CD4+ T cells in autoantibody-positive individuals with membranous nephropathy and of proteinase 3 and myeloperoxidase-specific CD4+ T cells in individuals with ANCA-associated GN. In summary, the results of our work will lead to a better understanding of autoreactive T cell mediated processes in renal damage and might identify potential targets for novel antigen-based treatment strategies for autoimmune kidney diseases.


  • The role of regulatory T cells in Experimental Autoimmune Glomerulonephritis.

    Klinge S, Yan K, Reimers D, Brede KM, Schmid J, Paust HJ, Krebs CF, Panzer U, Hopfer H, Mittrücker H-W. Am J Physiol Renal Physiol 2019 Mar

  • Adaptive immunity and IL-17A are not involved in the progression of chronic kidney disease after 5/6 nephrectomy in mice.

    Rosendahl A, Kabiri R, Bode M, Cai A, Klinge S, Ehmke H, Mittrücker HW, Wenzel UOBr J Pharmacol. 2018 Sep

  • Tissue-Resident Lymphocytes in the Kidney. 

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

  • Proliferation of Ly6C+ monocytes during urinary tract infections is regulated by IL-6 trans-signaling.

    Dixit A, Bottek J, Beerlage AL, Schuettpelz J, Thiebes S, Brenzel A, Garbers C, Rose-John S, Mittrücker H-W, Squire A, Engel DR.J Leukoc Biol. 2018 Jan

  • 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

  • CXCR3+ regulatory T cells control Th1 responses in crescentic GN.

    Paust HJ, Riedel JH, Krebs CF, Turner JE, Brix SR, Krohn S, Velden J, Wiech T, Kaffke A, Peters A, Bennstein SB, Kapffer S, Meyer-Schwesinger C, Wegscheid C, Tiegs G, Thaiss F, Mittrücker HW, Steinmetz OM, Stahl RA, Panzer U.J Am Soc Nephrol. 2016 Jul

III. Medizinische Klinik und Poliklinik
Universitätsklinikum Hamburg-Eppendorf

Martinistrasse 52
20246 Hamburg, Germany
Tel:   +49-40-7410-51557
Fax:  +49-40-7410-59036
This email address is being protected from spambots. You need JavaScript enabled to view it.