Author:
Yan Ji-Jing,Ryu Jung-Hwa,Piao Honglin,Hwang Ju Hee,Han Dongkyu,Lee Sun-Kyung,Jang Joon Young,Lee Joongyub,Koo Tai Yeon,Yang Jaeseok
Abstract
BackgroundGranulocyte colony-stimulating factor (G-CSF) can increase populations of myeloid-derived suppressor cells, innate immune suppressors that play an immunoregulatory role in antitumor immunity. However, the roles of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury remain unclear.MethodsWe used mouse models of ischemia-reperfusion injury to investigate whether G-CSF can attenuate renal injury by increasing infiltration of myeloid-derived suppressor cells into kidney tissue.ResultsG-CSF treatment before ischemia-reperfusion injury subsequently attenuated acute renal dysfunction, tissue injury, and tubular apoptosis. Additionally, G-CSF treatment suppressed renal infiltration of macrophages and T cells as well as renal levels of IL-6, MCP-1, IL-12, TNF-α, and IFN-γ, but it increased levels of IL-10, arginase-1, and reactive oxygen species. Moreover, administering G-CSF after ischemia-reperfusion injury improved the recovery of renal function and attenuated renal fibrosis on day 28. G-CSF treatment increased renal infiltration of myeloid-derived suppressor cells (F4/80−CD11b+Gr-1int), especially the granulocytic myeloid-derived suppressor cell population (CD11b+Ly6GintLy6Clow); splenic F4/80−CD11b+Gr-1+cells sorted from G-CSF–treated mice displayed higher levels of arginase-1, IL-10, and reactive oxygen species relative to those from control mice. Furthermore, these splenic cells effectively suppressedin vitroT cell activation mainly through arginase-1 and reactive oxygen species, and their adoptive transfer attenuated renal injury. Combined treatment with anti–Gr-1 and G-CSF showed better renoprotective effects than G-CSF alone, whereas preferential depletion of myeloid-derived suppressor cells by pep-G3 or gemcitabine abrogated the beneficial effects of G-CSF against renal injury.ConclusionsG-CSF induced renal myeloid-derived suppressor cells, thereby attenuating acute renal injury and chronic renal fibrosis after ischemia-reperfusion injury. These results suggest therapeutic potential of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury.
Publisher
American Society of Nephrology (ASN)
Subject
Nephrology,General Medicine
Cited by
27 articles.
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