SFB 1192

Project A8

Modulation of dendritic cells by CX3CR1 and complement receptors in crescentic glomerulonephritis

Kidney dendritic cells (DCs) are central regulators in crescentic glomerulonephritis (cGN). They modulate the response of infiltrating TH cells, thereby either driving or inhibiting the progression of GN, depending on their functional state. Kidney DCs can be identified by expression of MHC II and CD11c, a component of complement receptor 4. More than 90% of renal DC also express the CD11b, a component of complement receptor 3, and the chemokine receptor CX3CR1. While the functional roles of CD11c and CD11b in the kidney are unknown, we recently showed that CX3CR1 is required for the homeostatic and inflammatory recruitment of DCs to the kidney, but not to other organs.

In this proposal, we would like to clarify
1. Whether the dependence of kidney DCs on CX3CR1 depends on renal CX3CL1 expression and whether this chemokine contributes to the progression of cGN.
2. Whether pharmacological CX3CR1 blockade can attenuate cGN progression.
3. Whether complement receptors like CR3, CR4 and C5aR affect kidney DC functionality.
4. Whether these receptors affect the progression of cGN, and
5. Whether CX3CR1 and complement receptors are important for the homeostatic and inflammatory migration of DCs from the kidney to the renal LN and for induction of immunity. Our long-term aim is to explore the therapeutic potential of CX3CR1 and complement receptor inhibitors in cGN.

Publikationen

  • Protecting the kidney against autoimmunity and inflammation.

    Christian Kurts, Catherine Meyer-SchwesingerNat Rev Nephrol. 2018 Dec

  • 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

  • CD103+ Kidney Dendritic Cells Protect against Crescentic GN by Maintaining IL-10-Producing Regulatory T Cells.

    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

III. Medizinische Klinik und Poliklinik
Universitätsklinikum Hamburg-Eppendorf

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