LAUSR

We recently demonstrated that human T‐helper (Th) 17 cells, unlike Th1 cells, do not proliferate in response to T‐cell receptor stimulation, mainly because of their reduced capacity to produce and respond to IL‐2. In this study, we show that their lower responsiveness to IL‐2 is due to the selective expression of Musculin (MSC), a member of the basic helix‐loop‐helix transcription factors. We show that MSC expression in human Th17 cells is retinoic acid orphan receptor (ROR)γt‐dependent, and allows the upregulation of PPP2R2B, a regulatory member of the protein phosphatase 2A (PP2A) enzyme. High PPP2R2B levels in human Th17 cells were responsible for the reduced STAT5B Ser‐193 phosphorylation upon IL‐2 signalling and, therefore, impaired STAT5B DNA binding and transcriptional activity on IL‐2 target genes. PP2A, observed in Th17 cells, controls also STAT3, dephosphorylating Ser727, thus increasing its activity that plays a crucial role in Th17 development and/or maintenance. Thus, our findings identify an additional mechanism responsible for the limited expansion of human Th17 cells, and could provide a further explanation for the rarity of these cells in inflamed tissues.