Human "TH9" cells are a subpopulation of PPAR-γ+ TH2 cells.
Claire MicosséLeonhard von MeyennOliver SteckEnja KipferChristian AdamCedric SimillionSeyed Morteza Seyed JafariPeter OlahNikhil YawalkarDagmar SimonLuca BorradoriStefan KuchenDaniel YerlyBernhard HomeyCurdin ConradBerend SnijderMarc SchmidtChristoph SchlapbachPublished in: Science immunology (2020)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- transcription factor
- endoplasmic reticulum stress
- type diabetes
- signaling pathway
- cell death
- endothelial cells
- stem cells
- magnetic resonance imaging
- magnetic resonance
- hepatitis b virus
- insulin resistance
- intensive care unit
- bone marrow
- mesenchymal stem cells
- extracorporeal membrane oxygenation
- blood brain barrier
- acute respiratory distress syndrome
- pluripotent stem cells