Affordable Access

deepdyve-link
Publisher Website

Interleukin-1 accounts for intrarenal Th17 cell activation during ureteral obstruction.

Authors
  • Pindjakova, Jana
  • Hanley, Shirley A
  • Duffy, Michelle M
  • Sutton, Caroline E
  • Weidhofer, Gudrun A
  • Miller, Melinda N
  • Nath, Karl A
  • Mills, Kingston H G
  • Ceredig, Rhodri
  • Griffin, Matthew D
Type
Published Article
Journal
Kidney International
Publisher
Elsevier
Publication Date
Feb 01, 2012
Volume
81
Issue
4
Pages
379–390
Identifiers
DOI: 10.1038/ki.2011.348
PMID: 21975862
Source
Medline
License
Unknown

Abstract

Interleukin 17A-secreting T-helper 17 (Th17) cells are pathogenic in inflammatory kidney diseases, but their intrarenal regulation is poorly understood. In order to better define Th17 cell dynamics during interstitial inflammation, we utilized the mouse unilateral ureteral obstruction model to analyze inflammatory cell subtypes by multicolor flow cytometry and cell sorting and by effects on in vitro-generated Th17 cells. Interleukin 17A expression localized to CCR6(+)CCR4(+/-)CD4(+) T-cells and progressively increased in obstructed kidneys. The number of CCR6(+)CD4(+) T-cells increased over 10-fold by 72 h, were enriched for interleukin 17A production, and were highly proliferative based on in vivo bromodeoxyuridine incorporation. Secreted products of leukocytes isolated from obstructed kidneys enhanced the interleukin 17A production of in vitro-generated Th17 cells. This Th17-enhancing activity was identified as interleukin-1 produced by renal dendritic cells and monocytes. The in vivo validity of these findings was confirmed in mice lacking the interleulin-1 receptor and in mice treated with a recombinant interleukin-1 receptor antagonist, each of which exhibited reduced intrarenal Th17 activity compared with control mice. Thus, the inflamed kidney accumulates CCR6(+) Th17 cells that undergo activation and proliferation. Production of interleukin 1 family cytokines by resident dendritic cells and infiltrating monocytes enhances intrarenal Th17 activation in acute kidney injury.

Report this publication

Statistics

Seen <100 times