| First Author | Liu Y | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 14709 | PubMed ID | 28436428 |
| Mgi Jnum | J:250030 | Mgi Id | MGI:5923276 |
| Doi | 10.1038/ncomms14709 | Citation | Liu Y, et al. (2017) Neuronal IFN-beta-induced PI3K/Akt-FoxA1 signalling is essential for generation of FoxA1(+)Treg cells. Nat Commun 8:14709 |
| abstractText | Neurons reprogramme encephalitogenic T cells (Tenc) to regulatory T cells (Tregs), either FoxP3(+)Tregs or FoxA1(+)Tregs. We reported previously that neuronal ability to generate FoxA1(+)Tregs was central to preventing neuroinflammation in experimental autoimmune encephalomyelitis (EAE). Mice lacking interferon (IFN)-beta were defective in generating FoxA1(+)Tregs in the brain. Here we show that lack of neuronal IFNbeta signalling is associated with the absence of programme death ligand-1 (PDL1), which prevents their ability to reprogramme Tenc cells to FoxA1(+)Tregs. Passive transfer-EAE via IFNbeta-competent Tenc cells to mice lacking IFNbeta and active induced-EAE in mice lacking its receptor, IFNAR, in the brain (Nes(Cre):Ifnar(fl/fl)) result in defective FoxA1(+)Tregs generation and aggravated neuroinflammation. IFNbeta activates neuronal PI3K/Akt signalling and Akt binds to transcription factor FoxA1 that translocates to the nucleus and induces PDL1. Conversely, inhibition of PI3K/Akt, FoxA1 and PDL1 blocked neuronal ability to generate FoxA1(+)Tregs. We characterize molecular factors central for neuronal ability to reprogramme pathogenic T cells to FoxA1(+)Tregs preventing neuroinflammation. |
