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  • Review Article
  • Published:

Immune cells in experimental acute kidney injury

Nature Reviews Nephrology volume 11, pages 88–101 (2015)Cite this article

Subjects

Key Points

  • Various components of the innate and adaptive immune systems are implicated in the pathogenesis and repair of acute kidney injury (AKI)

  • The roles of individual immune cell types have been most thoroughly investigated in models of ischaemic AKI

  • Various immune cells traffic into the post-ischaemic kidney and show changes in phenotypes and numbers depending on the time course after establishment of ischaemic AKI

  • The roles of macrophages, renal dendritic cells and T regulatory cells differ according to the pathogenesis of AKI

  • Although numerous studies in animal models of AKI show therapeutic potential for modulating immune cells, big hurdles must be overcome before applying these findings to patients

  • Functions and interactions of specific immune cell types and humoral factors in AKI differ between human disease and animal models, and depend on the type and stage of injury

Abstract

Acute kidney injury (AKI) prolongs hospital stay and increases mortality in various clinical settings. Ischaemia–reperfusion injury (IRI), nephrotoxic agents and infection leading to sepsis are among the major causes of AKI. Inflammatory responses substantially contribute to the overall renal damage in AKI. Both innate and adaptive immune systems are involved in the inflammatory process occurring in post-ischaemic AKI. Proinflammatory damage-associated molecular patterns, hypoxia-inducible factors, adhesion molecules, dysfunction of the renal vascular endothelium, chemokines, cytokines and Toll-like receptors are involved in the activation and recruitment of immune cells into injured kidneys. Immune cells of both the innate and adaptive immune systems, such as neutrophils, dendritic cells, macrophages and lymphocytes contribute to the pathogenesis of renal injury after IRI, and some of their subpopulations also participate in the repair process. These immune cells are also involved in the pathogenesis of nephrotoxic AKI. Experimental studies of immune cells in AKI have resulted in improved understanding of the immune mechanisms underlying AKI and will be the foundation for development of novel diagnostic and therapeutic targets. This Review describes what is currently known about the function of the immune system in the pathogenesis and repair of ischaemic and nephrotoxic AKI.

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Figure 1: Experimental models of AKI.
Figure 2: Major effector cells of both innate and adaptive immune systems contribute to the establishment of renal injury in ischaemic AKI.
Figure 3: Immune modulation during the repair phase of ischaemic AKI is a key factor in determining the outcome of AKI.
Figure 4: Important immune cells in each phase of renal IRI.

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Acknowledgements

H.R.J. is supported by a grant from the Korean Health Technology Research & Development Project, Ministry of Health & Welfare, Republic of Korea (HI13C-1263-020,013), a grant from Samsung Biomedical Research Institute (GL1B22612), and a grant from the Korean Society of Nephrology (PHX1130221). H.R. is supported by the NIH, US National Kidney Foundation, and generous research support from Rogelio Miro, Anne Segerson and Stoney Stanfil.

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  1. Nephrology Division, Department of Medicine, Samsung Medical Centre, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul, 135-710, South Korea

    Hye Ryoun Jang

  2. Nephrology Division, Department of Medicine, Johns Hopkins University School of Medicine, Ross Building, Room 965, 720 Rutland Avenue, Baltimore, 21205, MD, USA

    Hamid Rabb

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H.R.J. wrote the manuscript and researched data for the article; H.R.J. and H.R. contributed equally to discussion of content, review and/or editing the manuscript before submission.

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Correspondence to Hamid Rabb.

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Jang, H., Rabb, H. Immune cells in experimental acute kidney injury. Nat Rev Nephrol 11, 88–101 (2015). https://doi.org/10.1038/nrneph.2014.180

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