Extended Data Fig. 9: Metabolic activation of CXCR6+ CD8 T cells triggers auto-aggression.
From: Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH
a, Phosphorylated proteins downstream of TCR signalling in IL-15-stimulated, acetate-exposed CXCR6+ CD8 T cells. b, Glycolysis in auto-aggressive CXCR6+ CD8 T cells (n = 3). c, Calcium influx in IL-15-stimulated CXCR6+ and CXCR6− CD8 T cells exposed to metabolites, cytokines or TLR ligands (n = 4). d, e, Extracellular ATP in primary mouse hepatocyte supernatant after 24 h treatment with palmitate (250 μM) or agonistic trimeric FasL, or coculture with auto-aggressive CD8 T cells (n = 3). f, g, Metabolite detection in liver tissue of mice fed a normal diet or CD-HFD by matrix-assisted laser desorption and ionization imaging. Scale bar, 500 μm (f). Exact minima, maxima, centres, bounds of box and whiskers and percentiles are presented in Source Data. h, P2RX7 expression in IL-15-stimulated CD44+CXCR6+ CD8 T cells. i, j, Calcium influx in CXCR6+ CD8 T cells after incubation with NAD (1 μM) (n = 5) or supernatants from d (n = 3) for 30 min. k, Representative cytotoxicity result of CD8 T cell auto-aggression in the presence of P2RX7 or PANX1 inhibition (n = 3). l, sALT at day 2 after transfer of auto-aggressive CD8 T cells and anti-P2RX7 nanobody (50 μg per mouse). Two independent experiments. m, Representative cytotoxicity result of antigen-specific, IL-15-stimulated and acetate-exposed CXCR6+ OT1 CD8 T cells against S8L-loaded hepatocytes. Exact P (a–e, i, j, l) and n (a, l) values are presented in Source Data. *P < 0.05, **P < 0.01, ****P < 0.0001. Two-way ANOVA with Tukey’s multiple comparison test (c, i, j), one-way ANOVA with Tukey’s (b, e, l) or with Dunnett’s (d) multiple comparison test and unpaired two-tailed t-test (a). In a–e, i, j, l data are mean ± s.e.m., error is reported as s.d.
