SFB 1192
Project A4
Tissue resident memory T cells in glomerulonephritis
CD4+ T cells are central for the development of crescentic glomerulonephritis (GN). During GN, T cells are recruited to the kidney, however, the course and severity of GN might also be influenced by the pre-existing T cells resident in the kidney. In a mouse model of Staphylococcus aureus infection, we observe an extensive bacterial infection of the kidney which causes a profound renal accumulation of TH17 cells. After the clearance of infection, elevated amounts of T cells remain in the kidney and acquire a tissue resident memory T cell (TRM cell) phenotype. Induction of GN in this mouse model, after the mice recovered from infection, leads to aggravated renal disease and preliminary results indicate a reactivation of kidney resident TH17 cells previously generated during the Staphylococcus aureus infection. On the basis of these observations, we hypothesize that a renal infection causes persistent changes in TRM-cell composition in the kidney. During GN, infection-induced renal TRM cells are reactivated by inflammatory signals and alter course and severity of GN. In this project, we will focus on the characteristics and function of renal TRM cells in infection and autoimmunity. We will combine mouse infection models with models for GN to analyze the response of renal TRM cells in vivo. In parallel, the function of resident T cell populations will be investigated in human kidney biopsies. Main topics will be: i) phenotype, function, and transcriptomic profile of resident renal T cells; ii) signals that lead to reactivation of renal T cells; and iii) mechanisms by which resident T cells cause aggravated GN. In conclusion, this study will increase our knowledge on the contribution of T cells to GN and will help to identify processes that can be therapeutically targeted.
Selected Publications:
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Type I interferon drives T cell cytotoxicity by upregulation of interferon regulatory factor 7 in autoimmune kidney diseases in mice.
Wang H, Engesser J, Khatri R, Schaub DP, Paust HJ, Sultana Z, Jauch-Speer SL, Peters A, Kaffke A, Bonn S, Huber TB, Mittrücker HW, Krebs CF, Panzer U, Asada N.Nat Commun. 2025 May
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The integrated stress response pathway controls cytokine production in tissue-resident memory CD4+ T cells.
Asada N, Ginsberg P, Paust HJ, Song N, Riedel JH, Turner JE, Peters A, Kaffke A, Engesser J, Wang H, Zhao Y, Khatri R, Gild P, Dahlem R, Diercks BP, Das S, Ignatova Z, Huber TB, Prinz I, Gagliani N, Mittrücker HW, Krebs CF, Panzer U. Nat Immunol. 2025 Apr
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Immune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis.
Engesser J, Khatri R, Schaub DP, Zhao Y, Paust HJ, Sultana Z, Asada N, Riedel JH, Sivayoganathan V, Peters A, Kaffke A, Jauch-Speer SL, Goldbeck-Strieder T, Puelles VG, Wenzel UO, Steinmetz OM, Hoxha E, Turner JE, Mittrücker HW, Wiech T, Huber TB, Bonn S, Krebs CF#, Panzer U. Nat Commun. 2024 Sep
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Kidney-resident innate-like memory γδ T cells control chronic Staphylococcus aureus infection of mice
Bertram T, Reimers D, Lory NC, Schmidt C, Schmid J, C Heinig L, Bradtke P, Rattay G, Zielinski S, Hellmig M, Bartsch P, Rohde H, Nuñez S, Rosemblatt MV, Bono MR, Gagliani N, Sandrock I, Panzer U, Krebs CF, Meyer-Schwesinger C, Prinz I, Mittrücker HWProc Natl Acad Sci U S A. 2023 Jan
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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
Project-Team
Project Leader
Prof. Dr. Hans-Willi Mittrücker
Prof. Dr. Nicola Gagliani
Co-Workers
Guido Rattay
Peter Bradtke
Joanna Schmid