Human "T H 9" cells are a subpopulation of PPAR-γ + T H 2 cells.

Although TH 1, TH 2, and TH 17 cells are well-defined TH cell lineages in humans, it remains debated whether IL-9-producing TH cells represent a bona fide "TH 9" 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 TH 2 lineage-associated transcription factors. In these cells, IL-9 production is activation dependent, transient, and accompanied by down-regulation of TH 2 cytokines, leading to an apparent "TH 9" phenotype. IL-9+ TH 2 cells can be distinguished from "conventional" TH 2 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 ("TH 9" priming) and is required for IL-9 production. In line with their identity as early activated TH 2 cells, IL-9+ TH 2 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 TH 2 cells that depend on PPAR-γ for full effector functions.