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Neurons can convert pathogenic T cells to anti-inflammatory FoxA1+ regulatory T cells (Tregs), which can ameliorate EAE, but the molecular mechanism is only partially understood. Liu et al. show that autocrine interferon β signalling induces PDL1 expression in neurons, which is essential for neurons to reprogramme pathogenic T cells to FoxA1+ Tregs.

Nature Communications 8: Article number: 14709 (2017); Published 24 April 2017; Updated 22 May 2017 The affiliation details for Marco Prinz are incorrect in this Article. The correct affiliation details for this author are given below: Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg 79106, Germany.

Neurons reprogramme encephalitogenic T cells (T enc ) to regulatory T cells (T regs ), either FoxP3 + T regs or FoxA1 + T regs . We reported previously that neuronal ability to generate FoxA1 + T regs was central to preventing neuroinflammation in experimental autoimmune encephalomyelitis (EAE). Mice lacking interferon (IFN)-β were defective in generating FoxA1 + T regs in the brain. Here we show that lack of neuronal IFNβ signalling is associated with the absence of programme death ligand-1 (PDL1), which prevents their ability to reprogramme T enc cells to FoxA1 + T regs . Passive transfer-EAE via IFNβ-competent T enc cells to mice lacking IFNβ and active induced-EAE in mice lacking its receptor, IFNAR, in the brain (Nes Cre :Ifnar fl/fl ) result in defective FoxA1 + T regs generation and aggravated neuroinflammation. IFNβ 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 + T regs . We characterize molecular factors central for neuronal ability to reprogramme pathogenic T cells to FoxA1 + T regs preventing neuroinflammation.