Extended Data Fig. 8: Dietary serine restriction impairs human NK cell function.
From: Species-specific serine metabolism differentially controls natural killer cell functions
(a) Relative serine abundance in serum of control diet or serine/glycine-free diet-fed C57/BL6 mice after 10 days on diet. (b) Number of NK cells per spleen of control or serine-restricted mice. (c) Distribution across maturation subsets of splenic NK cells from control or serine-restricted mice. (d, e) Percent specific lysis of MC38 tumour cells (d) and percent IFN-γ+ (e) splenic NK cells from control or serine-restricted mice, coloured by mouse sex. (f) MFI of indicated phosphoproteins in splenic NK cells from control or serine-restricted mice. (g) Relative serine abundance in serum of control diet or serine/glycine-free diet-fed NOG-hIL-15 mice after 10 days on diet. (h) Quantification of NK cell subset distribution of adoptively transferred human NK cells in control or serine/glycine-free diet-fed host mice 3 d post transfer. (i) Human NK cells per 100 μL of blood in control or serine/glycine-free diet-fed host mice 3 d post transfer. (j-l) Percent IFN-γ+ (j), percent CD107a+ (k), and proportion of tumour-conjugated NK cells (l) of adoptively transferred NTC-edited or PHGDHCRISPRa human NK cells from peripheral blood of control diet-fed host mice on D3 post-adoptive transfer. (m, n) Individual tumour curves for control or serine/glycine-restricted mice transferred with NTC NK cells (m) or NTC versus PHGDHCRISPRa human NK cells. Data represent mean ± SEM or paired mice receiving same human donor NK cells. Data are representative of (a) n = 5, (b-m) n = 8-9, and (n) n = 4 independent mice per group, with sex deaggregated data represented as (b, c, e, f) n = 5 male and 4 female mice per diet and (d) n = 5 male mice per diet, n = 4 female mice for control diet, and n = 3 female mice for ser/gly- diet. *p < 0.05, **p < 0.01, ****p < 0.0001 by (a, b, d, g) two-sided Student’s t-test, (c, e, f, h, i) two-way ANOVA, (i) one-way ANOVA, and (j-l) two-sided paired t-test. Exact p-values: (a) p = 0.0046; (b) p = 0.0097; (e) p < 0.0001; (g) p = 0.0044; (j) p = 0.0338.
