Immune-mediated diseases, such as crescentic glomerulonephritis (cGN), are driven by inappropriately regulated cellular and humoral immune responses leading to renal injury and decline in kidney function. However, mechanisms of immune regulation in cGN are less clear. In a mouse model of cGN, we have shown previously that Foxp3+ regulatory T cells (Tregs) suppress the pathogenic T cell response by production of IL-10. Recently, we demonstrated that the co-inhibitory PD-1/PD-L1 pathway promotes Treg function during cGN, which is crucial to control the inflammatory Th1 immune response. Interestingly, preliminary data suggest that also inflammatory CD8+ T cell responses are regulated by the PD-1/PD-L1 pathway during cGN. However, the phenotype, pathogenic relevance, biological function, and regulation of renal CD8+ T cell responses in cGN are still incompletely understood. Thus, our studies will address the following aims: 1.) Phenotype and function of CD8+ T cells in murine models of acute and chronic cGN. 2.) Regulation of inflammatory T cell responses by the co-inhibitory receptors PD-1 and TIGIT. 3.) Mechanisms of T cell activation and regulation by non-professional APCs from kidney and liver. 4.) Phenotypic characterization of renal CD8+ T cell subsets in cGN patients by single cell RNAseq and immunohistochemistry. Our studies will result in a better understanding of mechanisms involved in the pathology and regulation of local inflammatory immune responses in acute and chronic cGN that may result in the identification of novel therapeutic targets in cGN.
Breda PC, Wiech T, Meyer-Schwesinger C, Grahammer F, Huber TB, Panzer U, Tiegs G, Neumann K.Am J Physiol Renal Physiol. 2019 Apr
Neumann K, Ostmann A, Breda PC, Ochel A, Tacke F, Paust HJ, Panzer U, Tiegs G Sci Rep. 2019 Feb
Diefenhardt P, Nosko A, Kluger MA, Richter JV, Wegscheid C, Kobayashi Y, Tiegs G, Huber S, Flavell RA, Stahl RAK, Steinmetz OMJ Am Soc Nephrol. 2018
Kluger MA, Nosko A, Ramcke T, Goerke B, Meyer MC, Wegscheid C, Luig M, Tiegs G, Stahl RA, Steinmetz OM.Clin Exp Immunol. 2017 Apr
Nosko A, Kluger MA, Diefenhardt P, Melderis S, Wegscheid C, Tiegs G, Stahl RA, Panzer U, Steinmetz OMJ Am Soc Nephrol. 2017 Jan
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
Evers BD, Engel DR, Böhner AM, Tittel AP, Krause TA, Heuser C, Garbi N, Kastenmüller W, Mack M, Tiegs G, Panzer U, Boor P, Ludwig-Portugall I, Kurts CJ Am Soc Nephrol. 2016 Nov
Kluger MA, Meyer MC, Nosko A, Goerke B, Luig M, Wegscheid C, Tiegs G, Stahl RA, Panzer U, Steinmetz OM.J Am Soc Nephrol. 2016 Feb
Kluger MA, Melderis S, Nosko A, Goerke B, Luig M, Meyer MC, Turner JE, Meyer-Schwesinger C, Wegscheid C, Tiegs G, Stahl RA, Panzer U, Steinmetz OM.Kidney Int. 2016 Jan
Project Leader
Prof. Dr. Gisa Tiegs
Dr. Katrin Neumann
Martinistrasse 52
20246 Hamburg, Germany
Tel: +49-40-7410-51557
Fax: +49-40-7410-59036
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Martinistrasse 52
20246 Hamburg, Germany