IL-17A production by renal γδ T cells promotes kidney injury in crescentic GN

J Am Soc Nephrol. 2012 Sep;23(9):1486-95. doi: 10.1681/ASN.2012010040. Epub 2012 Jul 12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • Disease Models, Animal
  • Glomerulonephritis / metabolism*
  • Glomerulonephritis / pathology
  • Interleukin-17 / metabolism*
  • Interleukin-23 / metabolism
  • Kidney / metabolism*
  • Kidney / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Signal Transduction / physiology
  • Th17 Cells / pathology
  • Time Factors

Substances

  • Interleukin-17
  • Interleukin-23
  • Receptors, Antigen, T-Cell, gamma-delta