title: Depletion of kidney CD11c+ F4/80+ cells impairs the recovery process in ischaemia/reperfusion-induced acute kidney injury.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Myung-Gyu
authors.initials: MG
authors.lastname: Kim
authors.forename: Chang Su
authors.initials: CS
authors.lastname: Boo
authors.forename: Yoon Sook
authors.initials: YS
authors.lastname: Ko
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Won Yong
authors.initials: WY
authors.lastname: Cho
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.forename: Sang-Kyung
authors.initials: SK
authors.lastname: Jo
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen / Q000378:metabolism; D015153:Blotting, Western; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D039521:CD11c Antigen / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004002:Clodronic Acid / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D018836:Inflammation Mediators / Q000378:metabolism; D008081:Liposomes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D015398:Signal Transduction
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D050071:Bone Density Conservation Agents; D039521:CD11c Antigen; D018836:Inflammation Mediators; D008081:Liposomes; D004002:Clodronic Acid