Huang Q1, Niu Z1, Tan J2, Yang J3, Liu Y3, Ma H3, Lee VW4, Sun S1, Song X1, Guo M3, Wang Y4, Cao Q5.
1Research Center for Immunology, Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, China;
- 2Department of Nephrology, Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China;
- 3Department of Nephrology, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China; and.
- 4Centre for Transplant and Renal Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.
- 5Research Center for Immunology, Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, China; Centre for Transplant and Renal Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia qi.cao@sydney.edu.au.
Abstract
IL-25 is an important immune regulator that can promote Th2 immune response-dependent immunity, inflammation, and tissue repair in asthma, intestinal infection, and autoimmune diseases. In this study, we examined the effects of IL-25 in renal ischemic/reperfusion injury (IRI). Treating IRI mice with IL-25 significantly improved renal function and reduced renal injury. Furthermore, IL-25 treatment increased the levels of IL-4, IL-5, and IL-13 in serum and kidney and promoted induction of alternatively activated (M2) macrophages in kidney. Notably, IL-25 treatment also increased the frequency of type 2 innate lymphoid cells (ILC2s) and multipotent progenitor type 2 (MPP(type2)) cells in kidney. IL-25-responsive ILC2 and MPP(type2) cells produced greater amounts of Th2 cytokines that associated with the induction of M2 macrophages and suppression of classically activated (M1) macrophages in vitro. Finally, adoptive transfer of ILC2s or MPP(type2) cells not only reduced renal functional and histologic injury in IRI mice but also induced M2 macrophages in kidney. In conclusion, our data identify a mechanism whereby IL-25-elicited ILC2 and MPP(type2) cells regulate macrophage phenotype in kidney and prevent renal IRI.
J Am Soc Nephrol. 2015 Sep;26(9):2199-211. doi: 10.1681/ASN.2014050479. Epub 2015 Jan 2.
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