Extended Data Fig. 4: Hepatic CXCR6+FOXO1low CD8 T cell frequency correlates with liver damage in NASH mice and patients with NASH.
From: Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH
a–c, Hepatic CXCR6+FOXO1low CD8 T cells at 6, 9 and 12 months of feeding a CD-HFD, and correlation of FOXO1 expression levels in hepatic CD44+CD8 T cells with frequency of hepatic CXCR6+PD1high of CD44+ CD8 T cells from mice fed a CD-HFD, and with NAS. Four independent experiments. d, e, CXCR6 and CX3CR1 expression levels in sorted hepatic CD44+CXCR6− CD8 T cells from healthy mice fed a normal diet (n = 5) after 18 h of treatment with the FOXO1 inhibitor AS1842856. f, CXCR6 expression levels after FOXO1 overexpression (transduction with pMP71-Foxo1-eGFP or pMP71-eGFP) in sorted CXCR6+ CD8 T cells (n = 3). g, h, Correlation of sALT and NAS with FOXO1 expression in hepatic CD44+ CD8 T cells from b. i, Correlation of FOXO1 expression in liver CD69+ CD8 T cells with sALT in patients with NASH (n = 15 in total: n = 12 NASH; n = 3 normal liver tissue (NAS = 0)). j, CXCR6 expression quantified by qPCR with reverse transcription (RT–qPCR) in liver tissue of patients with NASH (NAS ≥ 5) (unaffected tissue, n = 6; tissue from patients with NASH, n = 7). k, l, Correlation of relative CXCR6 expression with sALT and NAS in patients with NASH (unaffected individuals, n = 6; patients with NASH, n = 10). m, Correlation of sALT with numbers of cells that are positive for CXCR6 per mm2 of liver tissue in patients with NASH (n = 18). Scale bar, 100 μm. Representative image of in situ hybridization for CXCR6 mRNA in liver of patients with low or high sALT. Exact P (e, f, j) and n (b, c, g, h) values are presented in Source Data. *P < 0.05, **P < 0.01, ****P < 0.0001. Coefficient of determination (R2) and statistical significance (P value) were determined using Pearson’s correlation (b, c, g–i, k–m). Unpaired two-tailed (f, j) and paired two-tailed t-test (e). In e, f, j, data are mean ± s.e.m., error is reported as s.d.
