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  • Year in Review
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IMMUNE-MEDIATED KIDNEY DISEASE IN 2018

Protecting the kidney against autoimmunity and inflammation

Numerous exciting studies that advanced our understanding of immune-mediated kidney disease were published in 2018. Whereas most of these studies analysed the role of pro-inflammatory mediators, several novel anti-inflammatory mechanisms were discovered that involve immune cells and mediators with previously unrecognized protective roles in renal disease.

Key advances

  • Glomerular podocytes reside in an immune-privileged site and so are protected from cytotoxic T lymphocytes (CTLs); disruption of Bowman’s capsule during glomerulonephritis renders podocytes susceptible to killing by CTLs2.

  • Fibrocytes are important producers of collagen for the repair of mechanical kidney injury, but can also contribute to renal fibrosis during chronic inflammation6.

  • Renal resident type 2 innate lymphoid cells (ILC2s) exert a potent protective function in renal ischaemia–reperfusion injury by producing amphiregulin and inducing M2 polarization8.

  • The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) also has anti-inflammatory effects that protect kidney tubular cells after ischaemia–reperfusion injury and rhabdomyolysis9.

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Fig. 1: Immune cells and their mediators in kidney injury.

References

  1. McKinney, E. F., Lee, J. C., Jayne, D. R. W., Lyons, P. A. & Smith, K. G. C. T cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature 523, 612–616 (2015).

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  2. Chen, A. et al. Bowman’s capsule provides a protective niche for podocytes from cytotoxic CD8+ T cells. J. Clin. Invest. 128, 3413–3424 (2018).

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  3. Heymann, F. et al. Kidney dendritic cell activation is required for progression of renal disease in a mouse model of glomerular injury. J. Clin. Invest. 119, 1286–1297 (2009).

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  6. Buchtler, S. et al. Cellular origin and functional relevance of collagen I production in the kidney. J. Am. Soc. Nephrol. 29, 1859–1873 (2018).

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  7. Riedel, J. H. et al. IL-33-mediated expansion of type 2 innate lymphoid cells protects from progressive glomerulosclerosis. J. Am. Soc. Nephrol. 28, 2068–2080 (2017).

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  8. Cao, Q. et al. Potentiating tissue-resident type 2 innate lymphoid cells by IL-33 to prevent renal ischemia-reperfusion injury. J. Am. Soc. Nephrol. 29, 961–976 (2018).

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  9. Stoppe, C. et al. The protective role of macrophage migration inhibitory factor in acute kidney injury after cardiac surgery. Sci. Transl Med. 10, eaan4886 (2018).

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  10. Djudjaj, S. et al. Macrophage migration inhibitory factor mediates proliferative GN via CD74. J. Am. Soc. Nephrol. 27, 1650–1664 (2016).

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Acknowledgements

The authors’ work was supported by the Deutsche Forschungsgemeinschaft grants SFB1192 (C.K. and C.M.S.) and SFBTR57 (C.K.), and by the European Union’s Horizon 2020 research and innovation programme, grant no. 668036- RELENT (C.K.).

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Correspondence to Christian Kurts or Catherine Meyer-Schwesinger.

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Kurts, C., Meyer-Schwesinger, C. Protecting the kidney against autoimmunity and inflammation. Nat Rev Nephrol 15, 66–68 (2019). https://doi.org/10.1038/s41581-018-0097-0

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