Fig. 5: CD8 T cells expressing high and low levels of IL-18Rα possess distinct transcriptomic profiles. | Nature Communications

Fig. 5: CD8 T cells expressing high and low levels of IL-18Rα possess distinct transcriptomic profiles.

From: High expression of interleukin-18 receptor alpha correlates with severe respiratory viral disease and defines T cells with reduced cytotoxic signatures

Fig. 5

a 1 × 105 CD45.1+ OT-I cells adoptively transferred into C57BL/6 mice. Mice were infected with 105 pfu of A/HK x 31-OVA i.n. and lungs were collected on 6 dpi and sorted for cells expressing high (IL-18Rαhi) and low-to-intermediate levels of IL-18Rα (IL-18Rαlo). Created in BioRender. Cabug, A. (2025) https://BioRender.com/q5po0oj. b Antigen-experienced OT-I cells were sorted as CD44+CD45.1+TCRVα2+, then sorted into IL-18Rαhi and IL-18Rαlo subpopulations. c Number of differentially expressed genes (DEG) between IL-18Rαhi and IL-18Rαlo OT-I cells. d Volcano plot showing the DEGs between IL-18Rαhi and IL-18Rαlo cells. Horizontal line indicates -log10(P = 0.05). e Heatmaps showing expression levels of select genes grouped according to functional clusters. Each square represents an individual mouse where the blue and orange bars represent paired IL-18Rαlo and IL-18Rαhi cells, respectively (n = 6). Z-score values are shown. f DEGs in each subpopulation were analysed for protein-protein interaction based on the calculation of a STRING interaction score. Bubble size is FDR and colour intensity represents the magnitude of the difference in gene expression between IL-18Rαhi and IL-18Rαlo subsets (STRING score>0.7). Red networks represent genes more highly expressed in IL-18Rαhi and blue gene networks are those more highly expressed in IL-18Rαlo. g DEGs were compared to the MSigDB hallmark gene sets. Bubble size corresponds to gene overlap and represents the number of DEGs enriched in gene set. Bubble colours show the -log10(adjusted P-value). h IFNγ intracellular cytokine staining of IL-18Rαlo and IL-18Rαhi CD8 T cells from lungs on day 6 following influenza virus infection following IL-12, IL-18 or IL-12 + IL-18 stimulation. Unstimulated negative control and PMA/I stimulated positive control were included. IFNγ production by IL-18Rαhi CD8 T cells (top); IFNγ production by IL-18Rαlo CD8 T cells (bottom), (n = 5, mean ± SD, one-way ANOVA, Kruskal-Wallis, Dunn’s multiple comparisons).

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