| Autor: |
Nicole L. Bertschi, Oliver Steck, Fabian Luther, Cecilia Bazzini, Leonhard von Meyenn, Stefanie Schärli, Angela Vallone, Andrea Felser, Irene Keller, Olivier Friedli, Stefan Freigang, Nadja Begré, Susanne Radonjic-Hoesli, Cristina Lamos, Max Philip Gabutti, Michael Benzaquen, Markus Laimer, Dagmar Simon, Jean-Marc Nuoffer, Christoph Schlapbach |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-13 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-38233-x |
| Popis: |
Abstract T helper 9 (TH9) 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 TH9 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 TH9 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 TH 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 TH9 cells. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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