PPAR-γ Regulates the Effector Function of Human T Helper 9 Cells by Promoting Glycolysis

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Apr 29

PMID 37120582

Authors

Nicole L Bertschi

Oliver Steck

Fabian Luther

Cecilia Bazzini

Leonhard von Meyenn

Stefanie Scharli

Angela Vallone

Andrea Felser

Irene Keller

Olivier Friedli

Stefan Freigang

Nadja Begre

Susanne Radonjic-Hoesli

Cristina Lamos

Max Philip Gabutti

Michael Benzaquen

Markus Laimer

Dagmar Simon

Jean-Marc Nuoffer

Christoph Schlapbach

Affiliations

Soon will be listed here.

Abstract

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.

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