title: Immature renal dendritic cells recruit regulatory CXCR6(+) invariant natural killer T cells to attenuate crescentic GN.
abstract: Immature renal dendritic cells (DCs) are protective early in murine crescentic GN, but the mechanisms underlying this protection are unknown. Here, depletion of DCs reduced the recruitment of invariant natural killer T (iNKT) cells, which attenuate GN, into the kidney in the early stage of experimental crescentic GN. More than 90% of renal iNKT cells expressed the chemokine receptor CXCR6, and renal DCs produced high amounts of the cognate ligand CXCL16 early after induction of nephritis, suggesting that renal DC-derived CXCL16 might attract protective CXCR6(+) iNKT cells. Consistent with this finding, CXCR6-deficient mice exhibited less iNKT cell recruitment and developed nephritis that was more severe, similar to the aggravated nephritis observed in mice depleted of immature DCs. Finally, adoptive transfer of CXCR6-competent NKT cells ameliorated nephritis. Taken together, these results suggest an immunoprotective mechanism involving immature DCs, CXCL16, CXCR6, and regulatory iNKT cells, which might stimulate the development of new therapeutic strategies for GN.
authors.affiliation: Universitätsklinikum Hamburg-Eppendorf, III Medizinische Klinik, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Riedel
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Paust
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Turner
authors.forename: André P
authors.initials: AP
authors.lastname: Tittel
authors.forename: Christian
authors.initials: C
authors.lastname: Krebs
authors.forename: Erik
authors.initials: E
authors.lastname: Disteldorf
authors.forename: Claudia
authors.initials: C
authors.lastname: Wegscheid
authors.forename: Gisa
authors.initials: G
authors.lastname: Tiegs
authors.forename: Joachim
authors.initials: J
authors.lastname: Velden
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker
authors.forename: Natalio
authors.initials: N
authors.lastname: Garbi
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Steinmetz
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
mesh_terms: D000818:Animals; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000378:metabolism*; D003713:Dendritic Cells / Q000502:physiology*; D005921:Glomerulonephritis / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054387:Receptors, CXCR / Q000378:metabolism*; D000075744:Receptors, CXCR6; D012756:Sheep
chemical_list: D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6