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

Although T(H)1, T(H)2, and T(H)17 cells are well-defined T-H cell lineages in humans, it remains debated whether IL-9-producing T-H cells represent a bona fide "T(H)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 T-H cells express the chemokine receptors CCR4 and CCR8, produce high levels of IL-5 and IL-13, and express T(H)2 lineage-associated transcription factors. In these cells, IL-9 production is activation dependent, transient, and accompanied by down-regulation of T(H)2 cytokines, leading to an apparent "T(H)9" phenotype. IL-9(+) T(H)2 cells can be distinguished from "conventional" T(H)2 cells based on their expression of the transcription factor PPAR-gamma. Accordingly, PPAR-gamma is induced in naive TH cells by priming with IL-4 and TGF-beta ("T(H)9" priming) and is required for IL-9 production. In line with their identity as early activated T(H)2 cells, IL-9(+) T(H)2 cells are found in acute allergic skin inflammation in humans. We propose that IL-9-producing T-H cells are a phenotypically and functionally distinct subpopulation of T(H)2 cells that depend on PPAR-gamma for full effector functions.