Fig. 6: Transcriptional profiling indicates broad costimulatory and TCR-cooperative functions of IL-33–ST2 signaling in T cells.

a–f, Differentiated CTLs, Th1 cells and Th2 cells were stimulated with IL-33 or left untreated for 2 h and subjected to RNA-seq analysis (n = 3 independent cultures per subset). a, experimental outline. b, heatmaps depicting differentially expressed genes in each T-cell subset (log₂ fold change > 1.0; P adjusted < 0.01). c–f, comparison of IL-33-stimulated and untreated T cells (2 h timepoint). c, Venn diagram illustrating the overlap in differentially regulated genes between CTLs, Th1 cells and Th2 cells. d, gene ontology biological process overrepresentation analysis of IL-33-induced genes shared among all subsets. e, expression of selected transcription factors, cytokines and chemokines, and TCR-regulated genes in each T-cell subset. f, gene set enrichment analysis of TCR-downstream genes in IL-33-stimulated versus unstimulated CTLs. g–k, P14 T cells (CD45.1⁺ CD45.2⁺) were adoptively cotransferred with Il1rl1^−/− P14 T cells (CD45.1⁺) into WT mice (CD45.2⁺). Recipients were infected with high- or low-affinity GP33-expressing LCMV-Cl13 and analyzed at d10 p.i. (high-affinity group: n = 7, low-affinity group: n = 6). g, experimental outline. h, counts of recovered P14 and Il1rl1^−/− P14 T cells. i, frequencies and counts of KLRG1⁺ CD127⁻ P14 cells. j, frequencies and counts of KLRG1⁻ CD127⁺ P14 cells. k, counts of endogenous NP_396-404-specific CTLs and KLRG1⁺ CD127⁻ or KLRG1⁻ CD127⁺ NP_396-404-specific CTLs. Data represent one (a–f) or two (g–k) independent experiments. Data are presented as mean ± standard deviation, with each dot representing one mouse (h–k). P value was determined using one-way ANOVA with Tukey’s post hoc test (h–j), two-tailed t-tests (k), two-sided Wald test with BH correction (b and e), one-sided hypergeometric test with BH correction (d) and two-sided permutation test with BH correction (f).

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