Two-photon microscopy is able to produce exquisite and informative functional images of cells and blood vessels in living animals or tissue,1 especially when combined with genetically-encoded indicators of cellular activity.2 Since these imaging techniques typically produce too much data to analyse manually, a number of automated or semi-automated image analysis approaches have been developed. However, even aside from the algorithms themselves, many factors can complicate analysis workflows.
Background & Aims
NK1.1+ TCRαβint CD1-restricted T (NKT) cells are a unique subset of T lymphocytes that are thought to have an immunoregulatory role in a wide range of diseases. Most mouse NKT cells express a T-cell receptor that contains an invariant Vα14Jα18 chain and recognizes antigenic glycolipids presented in association with MHC class Ib (CD1d) molecules. These invariant NKT cells (iNKT) have been implicated in cholestatic liver injury.
Methods
We examined the role of iNKT cells in liver injury associated with biliary obstruction in mice with ligations of the common bile duct.
Results
The number of activated iNKT cells increased markedly in the livers of mice following bile duct-ligation (BDL). Plasma alanine aminotransferase (ALT) levels, an indicator of liver injury, were significantly higher in iNKT cell–deficient (Jα18−/−) mice, compared to wild-type mice, following BDL. Photoimage analysis of histologic sections confirmed that more damage was present in the livers of in Jα18−/−mice; liver damage correlated with increases in keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2 (MIP-2) production as well as neutrophil sequestration. Liver injury was significantly reduced in Jα18−/−mice treated with anti-KC and anti-MIP-2 or rendered neutrophil-deficient before BDL. Similarly, Jα18−/−mice that were injected with iNKT cells before BDL exhibited significant decreases in neutrophil accumulation and liver damage.
Conclusion
These data document the role of iNKT cells in suppressing the neutrophil proinflammatory response and neutrophil-dependent cholestatic liver damage.
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