Depletion of kidney CD11c+ F4/80+ cells impairs the recovery process in ischaemia/reperfusion-induced acute kidney injury.
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.
Kim
Myung-Gyu
MG
Division of Nephrology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
Boo
Chang Su
CS
Ko
Yoon Sook
YS
Lee
Hee Young
HY
Cho
Won Yong
WY
Kim
Hyoung Kyu
HK
Jo
Sang-Kyung
SK
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
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D050071:Bone Density Conservation Agents; D039521:CD11c Antigen; D018836:Inflammation Mediators; D008081:Liposomes; D004002:Clodronic Acid