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Immune cell behaviour and dynamics in the kidney — insights from in vivo imaging

Nature Reviews Nephrology volume 18, pages 22–37 (2022)Cite this article

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Abstract

The actions of immune cells within the kidney are of fundamental importance in kidney homeostasis and disease. In disease settings such as acute kidney injury, anti-neutrophil cytoplasmic antibody-associated vasculitis, lupus nephritis and renal transplant rejection, immune cells resident within the kidney and those recruited from the circulation propagate inflammatory responses with deleterious effects on the kidney. As in most forms of inflammation, intravital imaging — particularly two-photon microscopy — has been critical to our understanding of immune cell responses in the renal microvasculature and interstitium, enabling visualization of immune cell dynamics over time rather than statically. These studies have demonstrated differences in the recruitment and function of these cells from those in more conventional vascular beds, and provided a wealth of information on the actions of blood-borne immune cells such as neutrophils, monocytes and T cells, as well as kidney-resident mononuclear phagocytes, in a range of diseases affecting different kidney compartments. In particular, in vivo imaging has furthered our understanding of leukocyte function within the glomerulus in acute glomerulonephritis, and in the tubulointerstitium and interstitial microvasculature during acute kidney injury and following transplantation, revealing mechanisms of immune surveillance, antigen presentation and inflammation in the kidney.

Key points

  • In the specialized microvasculature of the glomerulus, the behaviour of immune cells and the mechanisms by which they respond to inflammatory stimuli differ from that of immune cells in postcapillary venules.

  • Dynamic in vivo imaging studies have demonstrated that even in the absence of disease, leukocyte adherence and crawling on the endothelium of the glomerulus and the interstitial microvasculature is common and occurs constitutively.

  • Intravascular crosstalk between different types of immune cells has been defined in immune-mediated kidney diseases and in the context of transplant rejection.

  • Use of in vivo two-photon microscopy to understand these unusual mechanisms potentially allows exploitation of these features to develop new therapies for immune kidney disease and transplantation.

  • In the future, emerging imaging technologies may enable a more granular understanding of the mechanisms by which leukocytes participate in diseases of these unique microvascular beds.

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Fig. 1: Microscopy modalities for imaging the kidney.
Fig. 2: The basic paradigm of leukocyte recruitment in conventional vascular beds.
Fig. 3: Examples of intravital immune cell imaging in the kidney.
Fig. 4: Glomerular leukocyte trafficking and behaviour as revealed by in vivo imaging.
Fig. 5: Tubulointerstitial leukocyte trafficking and behaviour as revealed by in vivo imaging.

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Authors and Affiliations

  1. Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia

    A. Richard Kitching & Michael J. Hickey

  2. Departments of Nephrology and Paediatric Nephrology, Monash Medical Centre, Clayton, Victoria, Australia

    A. Richard Kitching

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  1. A. Richard Kitching
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The authors contributed equally to all aspects of the article.

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Correspondence to A. Richard Kitching.

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Nature Reviews Nephrology thanks M. Oberbarnscheidt and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Postcapillary venules

The section of the microvasculature that in conventional vascular beds supports leukocyte trafficking in health and disease.

Adhesion molecules

Cell surface molecules that mediate leukocyte recruitment in inflammation and are usually found on leukocytes and the endothelium.

Proliferative glomerulonephritis

Types of glomerulonephritis characterized by increased numbers of cells within glomeruli, including leukocytes.

Neutrophil extracellular traps

(NETs). Web-like structures comprising an admixture of nuclear and cytoplasmic contents that are extruded from neutrophils in host defence and in inflammation.

Cross presentation

The process by which some dendritic cells are able to engulf and process extracellular antigens before presenting them as peptide-MHC class I complexes to CD8+ T lymphocytes.

Third harmonic generation

A non-linear form of imaging used to detect unstained structures such as tissue interfaces, based on the simultaneous arrival at a point of focus of three photons of the same wavelength.

Tissue refractive index

A value reflecting the degree to which a ray of light is bent as it passes through a tissue, resulting from a change in its velocity.

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Kitching, A.R., Hickey, M.J. Immune cell behaviour and dynamics in the kidney — insights from in vivo imaging. Nat Rev Nephrol 18, 22–37 (2022). https://doi.org/10.1038/s41581-021-00481-9

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