Fig. 4: The PNP inhibitor foro suppresses inosine catabolism in Teff cells.
From: Inosine is an alternative carbon source for CD8+-T-cell function under glucose restriction
a, Diagram of the PNP inhibitor foro blocking the catabolism of [13C5]inosine into R1P and its subsequent entrance into the PPP, glycolysis and the Krebs cycle. The red diamonds denote the uniformly 13C-labelled positions of the ribose subunit of inosine. b,c, Active human T cells were incubated in [13C5]inosine-containing medium with or without foro for 24 h, extracted and analysed. as described in the Methods. for PPP metabolites (b) and glycolytic and Krebs cycle metabolites (c) by IC–UHR-FTMS and by 1D HSQC NMR for inosine. All symbols and abbreviations are as described in Fig. 2. Numbers on the x axes represent the numbers of 13C atoms in the given metabolites. Values represent mean ± s.e.m. (n = 3). *, **, and *** denote P < 0.05, 0.01 and 0.001, respectively. In b, **P = 0.0012, 0.0034, 0.0043 and 0.0064 for [13C5]inosine, [13C6]G6P, [13C6]Fruc6P and [13C7]Sed7P for [13C5]inosine versus [13C5]inosine + foro, respectively; ***P = 0.00096, 0.0002 and 0.000005 for [13C5]R5P, [13C6]G1P and [13C4]Ery4P for [13C5]inosine versus [13C5]inosine + foro, respectively. In c, *P = 0.0117; ***P = 0.0002; **P = 0.0087 for [13C3]PEP, [13C3]pyruvate and [13C3]lactate for [13C5]inosine versus [13C5]inosine + foro, respectively. Other P values are listed in Supplementary Table 2. Data were analysed by unpaired two-sided t-test (b,c). Sample size (n) represents biologically independent samples (b,c).
