Extended Data Fig. 3: Haem released due to the mitochondrial protein degradation instructs terminal differentiation.
From: Proteasome-guided haem signalling axis contributes to T cell exhaustion
a, Protein abundance of BACH2, BLIMP1, PI3K and mTOR in MDR/MGhigh and MDR/MGlow subsets treated with Oligomycin A, Antimycin A, and Mdivi-1 along with indicated concentration of MG132 (n = 3, except BACH2, 0.2 μM, n = 2; 0.4 μM, n = 2). b, Relative RH concentration in TCF1-eGFP+PD-1+TIM3− (TPEx), TCF1-eGFP−PD-1+TIM3+ (TIEx) and TCF1-eGFP−PD-1+TIM3+ (TTEx) P14 TILs (n = 5). c, RH concentration in indicated human T cell subsets (Tn, n = 6; Teff, n = 10; TPEx, n = 8; TTEx, n = 7; Tmem, n = 8). d, Relative RH concentration in TIF and paired serum from tumour-bearing mice (n = 6). e, Relative RH concentration in repetitively stimulated CD8+ T cells treated with indicated haemin concentration (n = 8). f, Cell expansion of repetitively stimulated CD8+ T cells treated with indicated haemin concentrations (n = 3). g-l, Representative flow plots of CTV (g), Nurr77-GFP (i) and CD44 (k) fluorescence intensity and the quantitative results of CTV (h), Nurr77-GFP (j) and CD44 (l) in repetitively stimulated CD8+ T cells treated with haemin (n = 3). m, PCA of bulk RNA-seq profiles from the indicated groups (n = 5). n, GO Biological Process gene set enrichment analysis of bulk RNA-seq from haemin-treated versus control cells. o, PCA of bulk ATAC-seq profiles from the indicated groups (n = 4). p-r, Representative flow plots of PD-1 (p), TCF-1 (q) and cytokine production (r) in expanded P14 cells from LCMV Armstrong-rechallenge. Data are representative of two (b, c) or three (f, h, j, l) independent experiments with similar results or are the cumulative results from three (a, d, e) independent experiments. Each symbol represents one individual. Data are means ± s.d. and were analysed by Wilcoxon signed-rank test (d), simple linear regression (a), or One-way ANOVA (b, c, e, f, h, j, l). TIF, tumour interstitial fluid; TPEx, Progenitor exhausted T; TIEx, Intermediate exhausted T; TTEx, Terminal exhausted T.
