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SFB 1192

Project A8

Myeloid immune cell subsets and the renal microenvironment in glomerulonephritis

This project addresses the roles and cross-talk of myeloid immune cells, including mononuclear phagocytes (MNP, expertise Kurts) and neutrophilic granulocytes (PMN, expertise new co-applicant von Vietinghoff), in crescentic glomerulonephritis (cGN). Our bioinformatic analysis of the first true spatiotemporal single cell sequencing (scRNASeq) dataset in a mouse cGN model that we generated during the previous CRC funding period uncovered potential new myeloid pathomechanisms that we wish to explore. Our proposed Aim 1 addresses MNP subsets. We showed that MNP are protective in early and detrimental at late cGN stages. Our scRNASeq identified MNP subsets distinguished by MGL2, CD169 and DC-SIGN. We will selectively deplete these subsets to determine their roles in cGN. Aim 2 will study PMN, which our scRNASeq interactome analysis revealed as actively cross-talking with MNP throughout the course of cGN. To study the role of PMN in cGN progression, the impact of their ablation and PMN-derived IL-23 or TNFα on MNP cross-talk will be tested. A marked electrolyte gradient characterizes the renal microenvironment. In the previous funding period, we reported systemic immunosuppressive functions of a high salt diet in renal antibacterial response. as well as local renal immunoenhancement by NaCl in the kidney medulla. Aim 3 will address how the mediator of Na+ signaling, Nfat5 in MNP, impacts on cGN development and whether or not pharmacologic salt gradient depletion can diminish cGN at different disease stages. Aim 4 will delineate how PMN interaction with MNP relates to disease severity in human kidney biopsies and study underlying mechanisms in human primary myeloid cells. By investigating myeloid cell, specifically PMN and MNP subtype interaction and their relation to the renal osmolyte gradient, our project aims at delineating organ- and stage-specific approaches to management of myeloid cell-driven inflammation in glomerulonephritis.

Publikationen

  • Kidney immunology from pathophysiology to clinical translation.

    Christian Kurts, Sibylle von Vietinghoff, Christian F Krebs, Ulf PanzerNat Rev Immunol. 2025 Jan

  • Immune tolerance against infused FVIII in hemophilia A is mediated by PD-L1+ Tregs

    Janine Becker-Gotot, Mirjam Meissner, Vadim Kotov, Blanca Jurado-Mestre, Andrea Maione, Andreas Pannek, Thilo Albert, Chrystel Flores, Frank A Schildberg, Paul A Gleeson, Birgit M Reipert, Johannes Oldenburg, Christian KurtsJ Clin Invest. 2022 Nov

  • Monocyte-derived macrophages aggravate pulmonary vasculitis via cGAS/STING/IFN-mediated nucleic acid sensing.

    Nina Kessler, Susanne F Viehmann, Calvin Krollmann, Karola Mai, Katharina M Kirschner, Hella Luksch, Prasanti Kotagiri, Alexander M C Böhner, Dennis Huugen, Carina C de Oliveira Mann, Simon Otten, Stefanie A I Weiss, Thomas Zillinger, Kristiyana Dobrikova, Dieter E Jenne, Rayk Behrendt, Andrea Ablasser, Eva Bartok, Gunther Hartmann, Karl-Peter Hopfner, Paul A Lyons, Peter Boor, Angela Rösen-Wolff, Lino L Teichmann, Peter Heeringa, Christian Kurts, Natalio GarbiJ Exp Med. 2022 Oct

  • Generation of an alpaca serum that induces immune-mediated crescentic glomerulonephritis in mice.

    Ermanila Dhana, Daniela Klaus, Alexander Böhner, Florian Schmidt, Sibylle von Vietinghoff, Peter Boor, Sonja Djudjaj, Christian KurtsJ Immunol Methods. 2022 Aug

  • Renal Denervation Exacerbates LPS- and Antibody-induced Acute Kidney Injury, but Protects from Pyelonephritis in Mice.

    Alexander M C Böhner, Alice M Jacob, Christoph Heuser, Natascha E Stumpf, Alexander Effland, Zeinab Abdullah, Catherine Meyer-Schwesiger, Sibylle von Vietinghoff, Christian Kurts J Am Soc Nephrol. 2021 Oct

  • Drawing a single-cell landscape of the human kidney in (pseudo)-space and time.

    Krebs CF, Schlitzer A, Kurts C.Kidney Int. 2020 May

  • A high-salt diet compromises antibacterial neutrophil responses through hormonal perturbation.

    Jobin K, Stumpf NE, Schwab S, Eichler M, Neubert P, Rauh M, Adamowski M, Babyak O, Hinze D, Sivalingam S, Weisheit C, Hochheiser K, Schmidt SV, Meissner M, Garbi N, Abdullah Z, Wenzel U, Hölzel M, Jantsch J, Kurts C Sci Transl Med. 2020 Mar

  • The chemokine receptor CX3CR1 reduces renal injury in mice with angiotensin II induced hypertension

    Ahadzadeh E, Rosendahl A, Czesla D, Steffens P, Prüßner L, Meyer-Schwesinger C, Wanner N, Paust H, Huber T, Stahl R, Wiech T, Kurts C, Seniuk A, Ehmke H, Wenzel UAm J Physiol Renal Physiol. 2018 Sep

  • Pro-longed IKKβ inhibition improves ongoing CTL antitumor responses by incapacitating regulatory T cells.

    Heuser C, Gotot J, Piotrowski EC, Philipp MS, Courrèges JF, Otte MS, Guo L, Schmid-Burgk JL, Hornung V, Heine AK, Knolle PA, Garbi N, Serfling E, Evaristo C, Thaiss F, Kurts C.Cell Rep. 2017 Oct

  • Fully automated evaluation of total glomerular num-ber and capillary tuft size in murine nephritic kidneys using lightsheet microscopy.

    Klingberg A, Hasenberg A, Ludwig-Portugall I, Medyukhina A, Männ L, Brenzel A, Engel DR, Figge MT, Kurts C, Matthias GunzerJ Am Soc Nephrol. 2017 Feb

  • Inhibitor of NFκB Kinase Subunit 2 Blockade Hinders the Initiation but Ag-gravates the Progression of crescentic glomerulonephritis.

    Gotot J, Piotrowski E, Otte MS, Tittel AP, Guo L, Yao C, Ziegelbauer K, Panzer U, Garbi N, Kurts C, Thaiss FJ Am Soc Nephrol. 2016 Jul

  • A NLRP3-specific inflammasome inhibitor potently attenuates crystal-induced kidney fibrosis in vivo.

    Ludwig-Portugall I,*, Bartok E,* Dhana E, Evers BDG, Primiano MJ, Hall PJ, Franklin BS, Hornung V, Hartmann G, Boor P, Latz E, Kurts C.Kidney Int 2016

  • The complement receptor C5aR1 contributes to renal damage but protects the heart in angiotensin II-induced hypertension. 

    Weiss S, Rosendahl A, Czesla D, Meyer-Schwesinger C, Stahl RA, Ehmke H, Kurts C, Zipfel PF, Köhl J, Wenzel UOAm J Physiol Renal Physiol. 2016 Jun

Project-Team

Project Leader
Prof. Dr. Christian Kurts
Prof. Dr. Sibylle von Vietinghoff

Co-Workers
Alexander Böhner
Susanne Viehmann
Isis Ludwig-Portugall
Katarzyna Jobin
Franziska Köhler
Fernando Verduzco