LAUSR

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. The actions of immune cells within the kidney are of fundamental importance to kidney homeostasis and disease. This Review describes how live imaging of the kidney microvasculature in animal models has advanced our understanding of leukocyte behaviour in healthy and diseased kidneys. 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. 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.