Depletion of kidney CD11c+ F4/80+ cells impairs the recovery process in ischaemia/reperfusion-induced acute kidney injury

Nephrol Dial Transplant. 2010 Sep;25(9):2908-21. doi: 10.1093/ndt/gfq183. Epub 2010 Apr 12.


Background: Recent studies provided evidence of the potential role of CD11c(+) F4/80(+) dendritic subset in mediating injury and repair. The purpose of this study was to examine the role of kidney CD11c(+) F4/80(+) dendritic subset in the recovery phase of ischaemia/reperfusion injury (IRI).

Methods: Following ischaemia/reperfusion (I/R), liposome clodronate or phosphate buffered saline (PBS) was administered, and on day 7 biochemical and histologic kidney damage was assessed. Activation and depletion of CD11c(+) F4/80(+) dendritic subset were confirmed by flow cytometry. Isolation of kidney CD11c(+) cells on days 1 and 7 with in vitro culture for measuring cytokines was performed to define functional characteristics of these cells, and adoptive transfer of CD11c(+) cells was also done.

Results: Following kidney IRI, the percentage of CD11c(+) F4/80(+) kidney dendritic cell subset that co-expresses maturation marker increased. Liposome clodronate injection after I/R resulted in preferential depletion of CD11c(+) F4/80(+) kidney dendritic subset, and depletion of these cells was associated with persistent kidney injury, more apoptosis, inflammation and impaired tubular cell proliferation. CD11c(+) F4/80(+) cell depletion was also associated with higher tissue levels of pro-inflammatory cytokines and lower level of IL-10, indicating the persistence of inflammatory milieu. Isolated kidney CD11c(+) cells on day 7 showed different phenotype with increased production of IL-10 compared with those on day 1. Adoptive transfer of CD11c(+) cells partially reversed impaired tissue recovery.

Conclusion: Our results suggest that kidney CD11c(+) F4/80(+) dendritic subset might contribute to the recovery process by dynamic phenotypic change from pro-inflammatory to anti-inflammatory with modulation of immune response.

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Apoptosis / drug effects
  • B7-1 Antigen / metabolism*
  • B7-2 Antigen / metabolism
  • Blotting, Western
  • Bone Density Conservation Agents / pharmacology
  • CD11c Antigen / metabolism*
  • Cell Proliferation / drug effects
  • Clodronic Acid / pharmacology
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Flow Cytometry
  • Inflammation Mediators / metabolism
  • Liposomes
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Reperfusion Injury / complications
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control*
  • Signal Transduction


  • B7-1 Antigen
  • B7-2 Antigen
  • Bone Density Conservation Agents
  • CD11c Antigen
  • Inflammation Mediators
  • Liposomes
  • Clodronic Acid