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. 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.