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

作者：Kim Myung Gyu; Boo Chang Su; Ko Yoon Sook; Lee Hee Young; Cho Won Yong; Kim Hyoung Kyu; Jo Sang Kyung^*

来源：Nephrology Dialysis Transplantation, 2010, 25(9): 2908-2921.

DOI：10.1093/ndt/gfq183

• acute kidney injury
• dendritic subset
• liposome clodronate
• recovery

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 CD1 le 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 C D I I e cells on days I 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.

• 出版日期2010-9