Abstract
Acute kidney injury (AKI) is a common clinical complication associated with high mortality in patients. Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis. Plasmacytoid dendritic cells (pDCs) are a unique DC subset that specializes in type I interferon (IFN) production. Here, we showed that pDCs rapidly infiltrated the kidney in response to AKI and contributed to kidney damage by producing IFN-α. Deletion of pDCs using DTRBDCA2 transgenic (Tg) mice suppressed cisplatin-induced AKI, accompanied by marked reductions in proinflammatory cytokine production, immune cell infiltration and apoptosis in the kidney. In contrast, adoptive transfer of pDCs during AKI exacerbated kidney damage. We further identified IFN-α as the key factor that mediated the functions of pDCs during AKI, as IFN-α neutralization significantly attenuated kidney injury. Furthermore, IFN-α produced by pDCs directly induced the apoptosis of renal tubular epithelial cells (TECs) in vitro. In addition, our data demonstrated that apoptotic TECs induced the activation of pDCs, which was inhibited in the presence of an apoptosis inhibitor. Furthermore, similar deleterious effects of pDCs were observed in an ischemia reperfusion (IR)-induced AKI model. Clinically, increased expression of IFN-α in kidney biopsies was observed in kidney transplants with AKI. Taken together, the results of our study reveal that pDCs play a detrimental role in AKI via IFN-α.
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Acknowledgements
This study was supported by grants from the National Natural Science Foundation of China (No: 81870462 and 81470990 to F. Ding; No: 91642112 to R.H.; and No: 31600715 to Y.L.L.); The Science and Technology Commission of Shanghai Municipality (No: 18140903300 to R.H.; No: 17441904200 and 19441909300 to F.D.); Shanghai Ninth People’s Hospital Clinical Research Program (No: JYLJ007 to F.D.); Shanghai Ninth People’s Hospital MDT Program (2017–1–019 to F.D.); Major Special Projects of the Ministry of Science and Technology (2018ZX10302207 to Y.L.L.); Development Project of Shanghai Peak Disciplines-Integrative Medicine (20180101 to Y.L.L.); Doctoral Innovation Fund Projects from Shanghai Jiao Tong University School of Medicine (BXJ201730 to B.D.); and Fundamental Research Program Funding of Ninth People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine (JYZZ082B to B.D.).
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F.D. and R.H. conceived and designed the research; B.D., Y.S., S.M., Q.C., W.J., B.L., T.Y. and P.H. performed the research; B.D., R.H. and F.D. analyzed the data; B.D. and Y.L. wrote the manuscript.
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Deng, B., Lin, Y., Chen, Y. et al. Plasmacytoid dendritic cells promote acute kidney injury by producing interferon-α. Cell Mol Immunol 18, 219–229 (2021). https://doi.org/10.1038/s41423-019-0343-9
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DOI: https://doi.org/10.1038/s41423-019-0343-9
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