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

Jana Pindjakova, Shirley A. Hanley, Michelle M. Duffy, Caroline E. Sutton, Gudrun A. Weidhofer, Melinda N. Miller, Karl A Nath, Kingston H G Mills, Rhodri Ceredig, Matthew D. Griffin

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)379-390
Number of pages12
JournalKidney International
Volume81
Issue number4
DOIs
StatePublished - Feb 2 2012

Fingerprint

Th17 Cells
Ureteral Obstruction
Interleukin-1
Interleukin-17
Kidney
Dendritic Cells
Monocytes
T-Lymphocytes
Interleukin-1 Receptors
Kidney Diseases
Bromodeoxyuridine
Acute Kidney Injury
Flow Cytometry
Leukocytes
Cytokines
Inflammation

Keywords

  • chemokine receptor
  • cytokines
  • inflammation
  • lymphocytes
  • obstructive nephropathy

ASJC Scopus subject areas

  • Nephrology

Cite this

Pindjakova, J., Hanley, S. A., Duffy, M. M., Sutton, C. E., Weidhofer, G. A., Miller, M. N., ... Griffin, M. D. (2012). Interleukin-1 accounts for intrarenal Th17 cell activation during ureteral obstruction. Kidney International, 81(4), 379-390. https://doi.org/10.1038/ki.2011.348

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

In: Kidney International, Vol. 81, No. 4, 02.02.2012, p. 379-390.

Research output: Contribution to journalArticle

Pindjakova, J, Hanley, SA, Duffy, MM, Sutton, CE, Weidhofer, GA, Miller, MN, Nath, KA, Mills, KHG, Ceredig, R & Griffin, MD 2012, 'Interleukin-1 accounts for intrarenal Th17 cell activation during ureteral obstruction', Kidney International, vol. 81, no. 4, pp. 379-390. https://doi.org/10.1038/ki.2011.348
Pindjakova J, Hanley SA, Duffy MM, Sutton CE, Weidhofer GA, Miller MN et al. Interleukin-1 accounts for intrarenal Th17 cell activation during ureteral obstruction. Kidney International. 2012 Feb 2;81(4):379-390. https://doi.org/10.1038/ki.2011.348
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. / Interleukin-1 accounts for intrarenal Th17 cell activation during ureteral obstruction. In: Kidney International. 2012 ; Vol. 81, No. 4. pp. 379-390.
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