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 2019 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. https://sonar.ch/global/documents/279003 eng info:eu-repo/semantics/altIdentifier/doi/10.1126/sciimmunol.aat5943 info:eu-repo/semantics/altIdentifier/pmid/30658968 Science immunology. - 2019 Cytokines Dermatitis, Allergic Contact Dermatitis, Atopic Humans PPAR gamma Psoriasis Th2 Cells Human "TH9" cells are a subpopulation of PPAR-γ+ TH2 cells. http://purl.org/coar/resource_type/c_6501