Fig. 4: Hyperglycaemia dysregulates lung DC metabolism and acetylation.

a, WT (n = 4) and Akita (n = 4) lung DC incubated with 11 mM ¹³C-glucose. Supernatant ¹³C-lactate, area under the curve, two-sided unpaired t-test. b, WT (n = 15) and Akita (n = 10) lung DC acetyl-CoA, two-sided unpaired t-test. c, WT lung cDC1 incubated with high (50 mM, n = 12)/normal (10 mM, n = 9) glucose or with BMS303141 in high (50 mM, n = 16)/normal (10 mM, n = 13) glucose, then co-cultured for 4 days with OT-I-CD8⁺ T cells in normal (10 mM) glucose (in the absence of inhibitor). CD8⁺ T cells, two-way ANOVA with Holm–Sidak correction. d, WT lung cDC1 incubated for 20 h with 10 mM dichloroacetate (DCA) (n = 12) or medium (n = 12), then co-cultured for 4 days with OT-I-CD8⁺ T cells in normal (10 mM) glucose (in the absence of inhibitor). CD8⁺ T cells, two-sided Mann–Whitney U-test. e, OT-I-CD8⁺ T cells incubated for 4 days with lung WT cDC1 (n = 15) or Pdk2–4^−/− cDC1 (n = 11). CD8⁺ T cells, two-sided unpaired t-test. f, H3K27ac immunoblot of lung DC from WT (n = 6) and Akita (n = 5) mice, two-sided unpaired t-test. g, Fluorescent activated cell sorting of lung WT (n = 6) and Akita (n = 6) H3K27ac⁺ DC, two-sided unpaired t-test. h, WT lung cDC1 incubated for 20 h with high (50 mM, n = 6)/normal (10 mM, n = 8) glucose, or with 10 mM ANA in high (50 mM, n = 8)/normal (10 mM, n = 8) glucose, then co-cultured for 4 days with OT-I-CD8⁺ T cells and normal (10 mM) glucose (in the absence of inhibitor). CD8⁺ T cells, two-way ANOVA with Holm–Sidak correction. i,j, WT and Akita mice intraperitoneally administered 5 mg kg⁻¹ ANA or vehicle (dimethyl sulfoxide, DM) for 5 days, followed by intratracheal administration of 50 μg of OVA + 50 μg poly I:C. 24 h later, lung DC were sorted and transferred to naïve WT mice: WT+DM DC (n = 28), Akita+DM DC (n = 23), Akita+ANA DC (n = 12 for i, n = 11 for j). 10 days later, recipient mice were administered 500 pfu PR8-OVA (SIINFEKL), analyzed at day 7, Kruskal–Wallis test with Dunn’s correction. i, Lung OVA-PR8 viral RNA. j, Lung CD8⁺ T cells. All P values are indicated in Supplementary Table 1. All data mean+s.e.m.