Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Institute of Clinical Chemistry, University of Bern, Bern, Switzerland.
Nat Commun. 2023 Apr 29;14(1):2471. doi: 10.1038/s41467-023-38233-x.
T helper 9 (T9) cells promote allergic tissue inflammation and express the type 2 cytokines, IL-9 and IL-13, as well as the transcription factor, PPAR-γ. However, the functional role of PPAR-γ in human T9 cells remains unknown. Here, we demonstrate that PPAR-γ drives activation-induced glycolysis, which, in turn, promotes the expression of IL-9, but not IL-13, in an mTORC1-dependent manner. In vitro and ex vivo experiments show that the PPAR-γ-mTORC1-IL-9 pathway is active in T9 cells in human skin inflammation. Additionally, we find dynamic regulation of tissue glucose levels in acute allergic skin inflammation, suggesting that in situ glucose availability is linked to distinct immunological functions in vivo. Furthermore, paracrine IL-9 induces expression of the lactate transporter, MCT1, in T cells and promotes their aerobic glycolysis and proliferative capacity. Altogether, our findings uncover a hitherto unknown relationship between PPAR-γ-dependent glucose metabolism and pathogenic effector functions in human T9 cells.
辅助性 T 细胞 9（T9）细胞促进过敏组织炎症，并表达 2 型细胞因子，IL-9 和 IL-13，以及转录因子，PPAR-γ。然而，PPAR-γ 在人类 T9 细胞中的功能作用仍然未知。在这里，我们证明 PPAR-γ 驱动激活诱导的糖酵解，这反过来又以 mTORC1 依赖的方式促进 IL-9 的表达，但不促进 IL-13 的表达。体外和体内实验表明，在人类皮肤炎症中，T9 细胞中的 PPAR-γ-mTORC1-IL-9 途径是活跃的。此外，我们发现急性过敏皮肤炎症中组织葡萄糖水平的动态调节，表明原位葡萄糖可用性与体内不同的免疫功能有关。此外，旁分泌 IL-9 诱导 T 细胞中乳酸转运蛋白 MCT1 的表达，并促进其有氧糖酵解和增殖能力。总之，我们的发现揭示了 PPAR-γ 依赖性葡萄糖代谢与人类 T9 细胞中致病性效应功能之间以前未知的关系。
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