Th1 differentiating signaling in the liver is dysregulated by Vα14<i>i</i>NKT cells deficiency during Fas mAb-induced FLF.

<p>(<b>a</b>) Serum ALT levels of naïve WT mice, Fas mAb-treated WT and Jα18^−/− mice at 4.5 h. (<b>b–d</b>) H & E staining of liver sections from naïve WT mice, Fas mAb-treated WT and Jα18^−/− mice at 4.5 h. Livers from Fas mAb-treated WT mice (<b>c</b>) showed extensive damage with destruction of hepatocytes and distortion of normal liver architecture. The hepatocytes show hemorrhagic necrosis (white arrows) and characteristic signs of apoptosis (black arrows) including chromatin condensation and cellular shrinkage. In comparison, livers from Fas mAb-treated Jα18^−/− mice showed only minimal damage and retained the normal architecture (<b>d</b>). Liver from a naïve WT mouse is illustrated in (<b>b</b>) for comparison. (<b>e</b>) Western blot analysis of active caspase 3, T-bet, pSTAT-1, nitrotyrosine and GAPDH expression in the liver of PBS-treated WT mice and agonistic Fas mAb-treated WT and Jα18^−/− mice at 4.5 h. (<b>f</b>) TUNEL staining of liver sections from WT and Jα18^−/− mice at 4.5 h after Fas mAb injection in which WT mice showed intense TUNEL staining characteristic of apoptosis whereas Jα18^−/− mice showed less/reduced TUNEL staining. (<b>g</b>) HPLC measurement of hepatic GSH levels in PBS-treated WT mice and Fas mAb-treated WT and Jα18^−/− mice at 4.5 h. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038051#pone.0038051.s001" target="_blank">Figure S1</a> in a and g are presented as mean ± s.e.m with <i>n</i> = 5 mice/group; *<i>P</i><0.05 by one-way analysis of variance followed by Newman-Kuels post hoc test. All experiments were conducted twice.