Extended Data Fig. 6: The effect of IPA on CD4 + T cell energy metabolism is mediated by the PPARβ/δ nuclear receptor, not the canonical AhR signalling pathway. | Nature Metabolism

Extended Data Fig. 6: The effect of IPA on CD4 + T cell energy metabolism is mediated by the PPARβ/δ nuclear receptor, not the canonical AhR signalling pathway.

From: Microbial metabolite indole-3-propionic acid drives mitochondrial respiration in CD4+ T cells to confer protection against intestinal inflammation

Extended Data Fig. 6: The effect of IPA on CD4 + T cell energy metabolism is mediated by the PPARβ/δ nuclear receptor, not the canonical AhR signalling pathway.

(A) Schematic diagram showing the principle of HepG2-Lucia AhR reporter cell line. Created with BioRender.com. (B) Heatmap showing AhR activity induced by different Tryptophan metabolites. Ficz: 10 ng/mL. n = 3. (C) Seahorse Mitostress assay curve of WT and AhR−/− CD4 + T cells in basal and CD3/CD28 activation state in the presence of DMSO and Ficz (10 ng/mL). (D) Basal and maximal respiration analysis of the condition above. For Panel (C) and (D), n = 6 for Con and CD3/CD28 group; n = 4 for Ficz and CD3/CD28+Ficz group. (E) Seahorse Mitostress assay curve of WT and AhR−/− CD4 + T cells in basal and CD3/CD28 activation state in the presence of DMSO and IPA (100, 1000 μM). (F) Basal and maximal respiration analysis of the condition above. For Panel (E) and (F), n = 6 for each except n = 4 for IPA100 and IPA1000 groups. (G) GSEA of proteomics showing that Glycolysis and MYC pathway were enriched in CD3/CD28 groups compared with CD3/CD28 + IPA1000 group. Label CD3: CD3/CD28 group; CIPA2: CD3/CD28 + IPA1000 group. (H) Seahorse Mitostress assay of CD4 + T cells cultured with/without CD3/CD28 activation in the presence of DMSO and GW501516 (5 μM). The curves showed basal condition and in the presence of the inhibitor GSK3787 in sequence in 6 h. (I) Basal and maximal respiration of CD4 + T cells generated from Mitostress assay treated with/without GW501516 in basal and CD3/CD28 activation state in the absence/presence of GSK3787 inhibitor. For Panel (H) and (I): n = 6 for Con and CD3/CD28 group; n = 4 for the other two. (J) Seahorse Mitostress assay of CD4 + T cells cultured with/without CD3/CD28 activation in the presence of DMSO and GW7647 (1 μM). The urves showed basal condition and in the presence of the inhibitor GW6471 in sequence in 6 h. (K) Basal and maximal respiration of CD4 + T cells generated from Mitostress assay treated with/without GW7647 in basal and CD3/CD28 activation state in the absence/presence of GW6471 inhibitor. For Panel (J) and (K): n = 6 for Con and CD3/CD28 group; n = 4 for the other two. All the panels except (A), (B) and (G) represent mean ± SEM. (D), (F), (I) and (K) were analysed by two-way ANOVA with multiple comparisons.

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