Liver Injury After Invariant NKT Cell Activation by Free Alpha-galactosylceramide and Alpha-galactosylceramide-loaded Dendritic Cells

Liver Injury After Invariant NKT Cell Activation by Free Alpha-galactosylceramide and Alpha-galactosylceramide-loaded Dendritic Cells:

Background/Aim: Both free alpha-galactosylceramide (αGalCer) and αGalCer-loaded dendritic cells (DCG) activate invariant natural killer T (iNKT) cells to varying degrees, with αGalCer inducing liver injury. We sought to evaluate liver injury by these two pathways. Materials and Methods: Mice were injected with αGalCer or DCG followed by analysis of serum alanine transaminase (ALT) activity levels, mortality and liver function. Results: While ALT levels were elevated after DCG in a tumor necrosis factor (TNF)-α-dependent manner, DCG did not cause lethal injury. More serious injury of liver CD31-positive endothelial cells (CD31⁺ EC) was observed in mice treated with αGalCer than with DCG. Furthermore, liver CD31⁺ EC of αGalCer-treated mice induced naïve liver lymphocytes to produce TNF-α. Conclusion: DCG treatment did not induce lethal liver injury. CD31⁺ EC may play an antigen-presenting role to iNKT cells after αGalCer treatment and may be a cause of lethal injury.



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