PPAR-γ regulates the effector function of human T helper 9 cells by promoting glycolysis.

Bertschi, Nicole L; Steck, Oliver; Luther, Fabian; Bazzini, Cecilia; von Meyenn, Leonhard; Schärli, Stefanie; Vallone, Angela; Felser, Andrea; Keller, Irene; Friedli, Olivier; Freigang, Stefan; Begré, Nadja; Radonjic-Hoesli, Susanne; Lamos, Cristina; Gabutti, Max Philip; Benzaquen, Michael; Laimer, Markus; Simon, Dagmar; Nuoffer, Jean-Marc and Schlapbach, Christoph (2023). PPAR-γ regulates the effector function of human T helper 9 cells by promoting glycolysis. Nature Communications, 14(1), p. 2471. Springer Nature 10.1038/s41467-023-38233-x

s41467-023-38233-x.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Endocrinology, Diabetology and Clinical Nutrition
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology
08 Faculty of Science > Department of Biology > Bioinformatics and Computational Biology

UniBE Contributor:

Bertschi, Nicole Leonie, Luther, Fabian Urs, Bazzini, Cecilia, von Meyenn, Karl-Leonhard, Schärli, Stefanie, Felser, Andrea Debora, Keller, Irene (B), Friedli, Olivier, Freigang, Stefan Bernd, Begré, Nadja, Radonjic, Susanne Irene, Lamos, Cristina, Gabutti, Max Philip, Benzaquen, Michael Joseph, Laimer, Markus, Simon, Dagmar, Nuoffer, Jean-Marc, Schlapbach, Christoph


600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology




Springer Nature




Pubmed Import

Date Deposited:

02 May 2023 11:02

Last Modified:

02 May 2023 11:10

Publisher DOI:


PubMed ID:






Actions (login required)

Edit item Edit item
Provide Feedback