Extended Data Fig. 12: Diabetes-induced hyperacetylation impairs lung DC.

a-c, WT (n = 5) and Akita (n = 5) mice intravenously administered 5 mM 2-NBDG. Frequency of 2-NBDG⁺ cells within immune cell compartments, two-sided unpaired t-test. d, WT lung cDC1 incubated with high (50mM) or normal (10mM) glucose and BMS303141 for 20h, then co-cultured for 4 days with OT-I-CD8⁺ T cells in normal (10mM) glucose (in the absence of BMS303141): High glucose+DMSO (n = 12), normal glucose+DMSO (n = 9), high glucose+BMS303141 (n = 16), normal glucose+BMS303141 (n = 9). Frequency of Ki-67⁺CD8⁺ T cells, two-way ANOVA and Holm-Sidak correction. e-f, WT lung cDC2 incubated with high (50mM) or normal (10mM) glucose and BMS303141 for 20h, then co-cultured for 4 days with OT-I CD8⁺ T cells in normal (10mM) glucose (in the absence of BMS303141): High glucose+DMSO (n = 8), normal glucose+DMSO (n = 7), high glucose+BMS303141 (n = 8), normal glucose+BMS303141 (n = 8), two-way ANOVA and Holm-Sidak correction. e, CD8⁺ T cells. f, Ki-67⁺CD8⁺ T cells. g-h, WT lung DC incubated with 10 mM DCA (n = 12) or vehicle (n = 12) for 20h, then co-cultured for 4 days with OT-I-CD8⁺ T cells in normal (10mM) glucose. g, CD8⁺ T cells, co-cultured with cDC2, two-sided Mann-Whitney U-test. h, IFNγ⁺CD8⁺ T cells, co-cultured with cDC1, two-sided unpaired t-test, IFNγ⁺CD8⁺ T cells, co-cultured with cDC2, two-sided Mann-Whitney U-test. i-k, OT-I-CD8⁺ T cells, co-cultured for 4 days with lung WT cDC1 (n = 15), WT cDC2 (n = 15), Pdk2-4^−/− cDC1 (n = 11) or Pdk2-4^−/− cDC2 (n = 12), two-sided unpaired t-test. i, CD8⁺ T cells, co-cultured with cDC2. j, IFNγ⁺CD8⁺T cells, and k, Ki-67⁺CD8⁺ T cells, cocultured with cDC1 and cDC2. l-m, CUT&Tag chromatin profiling of lung DC from naïve WT and Akita mice. Scatter plots with mean normalized reads in peaks in WT and Akita, red lines x = y. l, H3K27ac. m, H3K27me3. n, Flow cytometry of lung DC, representative histograms of H3K27ac. o-s, WT Lung DC incubated with high (50mM) or normal (10mM) glucose and 10mM ANA for 20h, then co-cultured for 4 days with OT-I CD8⁺ T cells in normal (10mM) glucose (in the absence of inhibitor), two-way ANOVA and Holm-Sidak correction. o-p, cDC1 incubated with high (50mM) glucose+DM (n = 6), normal (10mM) glucose+DM (n = 8), high (50mM) glucose+ANA (n = 8), normal (10mM) glucose+ANA (n = 8). o, Ki-67⁺CD8⁺ T cells. p, IFNγ⁺CD8⁺ T cells. q-s, cDC2 incubated with high (50mM) glucose+DM (n = 9), normal (10mM) glucose+DM (n = 8), high (50mM) glucose+ANA (n = 8), normal (10mM) glucose+ANA (n = 8). q, CD8⁺ T cells. r, Ki-67⁺CD8⁺ T cells. s, IFNγ⁺CD8⁺ T cells. t-w, WT and Akita mice infected with 50pfu PR8 and administered 5 mg/kg ANA or DMSO daily from 3 days before infection, analyzed at 10 d.p.i.: WT+DMSO (n = 12), WT+ANA (n = 12), Akita+DMSO (n = 13), Akita+ANA (n = 14), pooled data from 2 experiments. t, cDC1, Kruskal Wallis with Dunn’s correction. u, cDC2, Kruskal Wallis test with Dunn’s correction. v, CD64⁺ DC, one-way ANOVA with Holm-Sidak. w, Ki-67⁺cDC1, one-way ANOVA with Holm-Sidak. x-z, Mice intraperitoneally administered STZ or PBS, then infected with 50pfu PR8 and administered 5 mg/kg ANA/vehicle (DM) daily from 3 days before infection, analyzed at 10 d.p.i.: PBS+DM (n = 13), PBS+ANA (n = 10), STZ+DM (n = 10), STZ+ANA (n = 11), pooled data from 2 experiments. x, cDC1, Kruskal Wallis with Dunn’s correction. y, cDC2, one-way ANOVA with Holm-Sidak. z, CD64⁺ DC, one-way ANOVA with Holm-Sidak. All data mean+s.e.m. AM, Alveolar macrophage.