IL-17A production by renal γδ T cells promotes kidney injury in crescentic GN.
The Th17 immune response appears to contribute to the pathogenesis of human and experimental crescentic GN, but the cell types that produce IL-17A in the kidney, the mechanisms involved in its induction, and the IL-17A-mediated effector functions that promote renal tissue injury are incompletely understood. Here, using a murine model of crescentic GN, we found that CD4(+) T cells, γδ T cells, and a population of CD3(+)CD4(-)CD8(-)γδT cell receptor(-)NK1.1(-) T cells all produce IL-17A in the kidney. A time course analysis identified γδ T cells as a major source of IL-17A in the early phase of disease, before the first CD4(+) Th17 cells arrived. The production of IL-17A by renal γδ T cells depended on IL-23p19 signaling and retinoic acid-related orphan receptor-γt but not on IL-1β or IL-6. In addition, depletion of dendritic cells, which produce IL-23 in the kidney, reduced IL-17A production by renal γδ T cells. Furthermore, the lack of IL-17A production in γδ T cells, as well as the absence of all γδ T cells, reduced neutrophil recruitment into the kidney and ameliorated renal injury. Taken together, these data suggest that γδ T cells produce IL-17A in the kidney, induced by IL-23, promoting neutrophil recruitment, and contributing to the immunopathogenesis of crescentic GN.
Universitätsklinikum Hamburg-Eppendorf, III Medizinische Klinik, Martinistrasse 52, 20246 Hamburg, Germany.
Jan-Eric
JE
Turner
Christian
C
Krebs
Andre P
AP
Tittel
Hans-Joachim
HJ
Paust
Catherine
C
Meyer-Schwesinger
Sabrina B
SB
Bennstein
Oliver M
OM
Steinmetz
Immo
I
Prinz
Tim
T
Magnus
Thomas
T
Korn
Rolf A K
RA
Stahl
Christian
C
Kurts
Ulf
U
Panzer
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D058504:Th17 Cells / Q000473:pathology; D013997:Time Factors
D020381:Interleukin-17; D053759:Interleukin-23; D016692:Receptors, Antigen, T-Cell, gamma-delta