Human

Micossé C; von Meyenn L; Steck O; Kipfer E; Adam C; Simillion C; Seyed Jafari SM; Olah P; Yawlkar N; Simon D; Borradori L; Kuchen S; Yerly D; Homey B; Conrad C; Snijder B; Schmidt M; Schlapbach C

doi:10.1126/sciimmunol.aat5943

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Journal article

Human "TH9" cells are a subpopulation of PPAR-γ+ TH2 cells.

Micossé C Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
von Meyenn L Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Steck O Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Kipfer E Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Adam C Department of Dermatology, University Hospital Würzburg, Würzburg, Germany.
Simillion C Interfaculty Bioinformatics Unit and SIB Swiss Institute of Bioinformatics, University of Bern, Bern, Switzerland.
Seyed Jafari SM Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Olah P Department of Dermatology, University Hospital Düsseldorf, Düsseldorf, Germany.
Yawlkar N Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Simon D Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Borradori L Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Kuchen S Department of Rheumatology, Immunology and Allergology, Bern University Hospital, University of Bern, Bern, Switzerland.
Yerly D Department of Rheumatology, Immunology and Allergology, Bern University Hospital, University of Bern, Bern, Switzerland.
Homey B Department of Dermatology, University Hospital Düsseldorf, Düsseldorf, Germany.
Conrad C Department of Dermatology, University Hospital CHUV, Lausanne, Switzerland.
Snijder B Institute of Molecular Systems Biology, ETH, Zurich, Switzerland.
Schmidt M Department of Dermatology, University Hospital Würzburg, Würzburg, Germany.
Schlapbach C Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. christoph.schlapbach@insel.ch.

2019-01-20

Published in:

Science immunology. - 2019

English Although TH1, TH2, and TH17 cells are well-defined TH cell lineages in humans, it remains debated whether IL-9-producing TH cells represent a bona fide "TH9" lineage. Our understanding of the cellular characteristics and functions of IL-9-producing TH cells in humans is still nascent. Here, we report that human IL-9-producing TH cells express the chemokine receptors CCR4 and CCR8, produce high levels of IL-5 and IL-13, and express TH2 lineage-associated transcription factors. In these cells, IL-9 production is activation dependent, transient, and accompanied by down-regulation of TH2 cytokines, leading to an apparent "TH9" phenotype. IL-9+ TH2 cells can be distinguished from "conventional" TH2 cells based on their expression of the transcription factor PPAR-γ. Accordingly, PPAR-γ is induced in naïve TH cells by priming with IL-4 and TGF-β ("TH9" priming) and is required for IL-9 production. In line with their identity as early activated TH2 cells, IL-9+ TH2 cells are found in acute allergic skin inflammation in humans. We propose that IL-9-producing TH cells are a phenotypically and functionally distinct subpopulation of TH2 cells that depend on PPAR-γ for full effector functions.

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