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