Research ArticleHELPER T CELLS

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

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Science Immunology  18 Jan 2019:
Vol. 4, Issue 31, eaat5943
DOI: 10.1126/sciimmunol.aat5943

Licensing interleukin-9 production

Whereas the biological roles of T helper 1 (TH1), TH2, and TH17 cells are reasonably well established, the functions of interleukin-9 (IL-9)–secreting TH9 cells remains elusive. Several studies have documented the presence of TH9 cells in both humans and mice. Here, by studying human TH cells ex vivo, Micossé et al. propose that TH9 cells are a subpopulation of TH2 cells that transiently up-regulate IL-9 and report the transcription factor peroxisome proliferator–activated receptor–γ (PPAR-γ) to be a key regulator of IL-9 production. The results presented by Micossé et al. call for a closer examination of the ontogeny of IL-9–producing TH cells using cytokine reporter mouse strains.


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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