Extended Data Fig. 9: Hyperglycaemia protects from allergic lung inflammation.
From: Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes
a-c, WT and Akita mice intratracheally administered 10μg HDM at day 0, 7-11, analyzed at day 14. a, Lung eosinophils and neutrophils, WT (n = 5) and Akita (n = 6) mice, two-sided Mann Whitney U-test. b, Lung PAS staining and mucus quantification,WT (n = 13) and Akita (n = 9) mice, two-sided Mann Whitney U-test. c, Lung CD4+ T cells and CD8+ T cells, WT (n = 5) and Akita (n = 6) mice, two-sided unpaired t-test. d-e, STZ (n = 4)- or PBS (n = 9)-pretreated mice intratracheally received 10μg HDM at day 0, 7-11, analyzed on day 14. d, Lung eosinophils and neutrophils. e, Lung CD4+ T cells and CD8+ T cells. f, WT lung cDC2 incubated in vitro with high (50mM, n = 7) or normal (10mM, n = 7) glucose for 20 h, then co-cultured for 4 days with OT-I-CD8+ T cells in normal (10mM) glucose. CD8+T cells, two-sided Mann-Whitney U-test. g, WT lung cDC2 incubated in vitro with high (50mM, n = 12) or normal (10mM, n = 12) glucose for 20 h, then co-cultured for 4 days with OT-II-CD4+ T cells in normal (10mM) glucose. CD4+ T cells, two-sided unpaired t-test. h-i, T cell activation by anti-CD3 and anti-CD28 in the presence of high (50mM, n = 8) or normal (10mM, n = 8) glucose, analyzed at day 4. h, CD8+ T cells, two-sided unpaired t-test. i, CD4+ T cells, two-sided Mann-Whitney U-test. j-r, WT mice sublethally irradiated and transplanted with a Zbtb46-DTR bone marrow, followed, after 8 weeks, by administration of STZ or PBS. 2 weeks later, mice infected with 50pfu PR8 and treated, every other day, with PBS or DT: PBS+PBS (n = 10), PBS+DT (n = 10), STZ+PBS (n = 12) and STZ+DT (n = 8). j, Lung PR8 viral titer, Kruskall Wallis test and Dunn’s correction. k, Lung virus-specific NP34 Tetramer+CD8+ T cells, Kruskall Wallis test and Dunn’s correction. l, Lung CD4+ T cells, Kruskall Wallis test and Dunn’s correction. m, Lung CD8+ T cells, one-way ANOVA and Holm-Sidak correction. n, Lung B cells, Kruskall Wallis test and Dunn’s correction. o, Lung GC B cells, Kruskall Wallis test and Dunn’s correction. p, Lung cDC1, Kruskall Wallis test and Dunn’s correction. q, Lung cDC2, Kruskall Wallis test and Dunn’s correction. r, Lung CD64+ DC, Kruskall Wallis test and Dunn’s correction. s-x, WT and Akita mice intratracheally administered 100μg HDM, followed, 24 h later, by DC sorting and transfer to WT recipients (receiving WT DC (n = 9), Akita DC (n = 10), or no DC (n = 7)). Recipient mice intratracheally challenged by 10μg HDM daily from day 7-11, analyzed at day 14. s, Lung eosinophils and neutrophils, Kruskall Wallis test and Dunn’s correction. t, Lung T cells, one-way ANOVA and Holm-Sidak correction. u, Lung Ly-6Chigh and Ly-6Clowmonocytes, one-way ANOVA and Holm-Sidak correction. v, Lung cDC1, Kruskal Wallis test with Dunn’s correction. w, Lung cDC2, one-way ANOVA and Holm-Sidak correction and CD64+ DC, Kruskal Wallis test with Dunn’s correction. x, CD4+ T cell IL-5 and IL-13 expression, Kruskall Wallis test and Dunn’s correction, and CD4+ T cell IFNγ expression, one-way ANOVA and Holm-Sidak correction. All data mean+s.e.m. PAS, Periodic acid-schiff; DT, diphtheria toxin.
