001 Effector functions of human TH9 cells depend on PPARγ-regulated glucose metabolism
نویسندگان
چکیده
TH9 cells, a subpopulation of TH2 are crucial mediators allergic skin inflammation. They characterized by expression IL-9/IL-9R and rely on the transcription factor PPARγ for full effector function. The functional role in however, remains unknown. Pathway analysis RNA-seq data from PPARγ-inhibited cells revealed concerted downregulation genes associated with T cell activation, glucose metabolism, aerobic glycolysis. Accordingly, featured higher glycolytic activity as compared to TH1 cells. In turn, impairment glycolysis led IL-9, but not IL-13 expression, thus emulating effects antagonism cytokine production. Conversely, enhancing increasing availability increased IL-9 levels, while leaving unchanged. Mechanistically, PPARγ- glycolysis-dependent regulation was mediated through mTORC1. Collectively, these observations indicated dichotomous regulatory activated that is dependent PPARγ-regulated via vitro ex vivo studies samples contact dermatitis this PPARγ/mTORC1/IL-9 pathway active pTH2 human Additionally, we found tissue levels were dynamically regulated acute inflammation, suggesting situ might be linked distinct immunological signals vivo. summary, our propose positive regulator metabolism specifically cellular metabolic activity. These findings highlight novel link between environment during inflammation type 2-driven
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2022
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2022.09.010